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Background: Most anticancer drugs possess the capacity to control precise molecular processes and gene-regulated protein expressions, which could enhance the efficacy of cancer treatments. Hirudinaria manillensis is prevalent in South Asia and has been employed for several decades in medical conditions based on its curative benefits. Methods and results: The present study aimed to explore the molecular regulation of the target EGFR gene, and the protein expression of EGFR on the HeLa cell line. To achieve our aim, quantitative real-time PCR and immunocytochemistry assays were conducted. Interestingly, qRT-PCR results confirmed the downregulation of the EGFR gene on the HeLa cells in comparison with the β- actin internal control gene. Furthermore, immunocytochemistry assay results confirmed the decreasing level of EGFR gene expression in the HeLa cells. Conclusion: Therefore, Hirudinaria manillensis could be a promising anticancer candidate for cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Mammalian cell lines devoid of mitochondrial DNA (mtDNA) are indispensable in studies aimed at elucidating the contribution of mtDNA to various cellular processes or interactions between nuclear and mitochondrial genomes. However, the repertoire of tools for generating such cells (also known as rho-0 or ρ0 cells) remains limited, and approaches remain time- and labor-intensive, ultimately limiting their availability. Ethidium bromide (EtBr), which is most commonly used to induce mtDNA loss in mammalian cells, is cytostatic and mutagenic as it affects both nuclear and mitochondrial genomes. Therefore, there is growing interest in new tools for generating ρ0 cell lines. Here, we examined the utility of 2′,3′-dideoxycytidine (ddC, zalcitabine) alone or in combination with EtBr for generating ρ0 cell lines of mouse and human origin as well as inducing the ρ0 state in mouse/human somatic cell hybrids. We report that ddC is superior to EtBr in both immortalized mouse fibroblasts and human 143B cells. Also, unlike EtBr, ddC exhibits no cytostatic effects at the highest concentration tested (200 μM), making it more suitable for general use. We conclude that ddC is a promising new tool for generating mammalian ρ0 cell lines. [ABSTRACT FROM AUTHOR]

To demonstrate the effect of silicon dioxide, citric acid and sodium selenite combination vaginal gel (DeflaGyn®) on critical parameters in carcinogenesis in vitro HeLa cell culture medium. Various parameters including cell viability, intracellular reactive oxygen species, genotoxicity, apoptosis, mitochondrial membrane potential and glutathione levels were evaluated by applying varying doses of vaginal gel to HeLa cell culture medium. The vaginal gel showed a dose-dependent cytotoxic effect on HeLa cells. The IC50 (half maximal inhibitory concentration) gel concentration for HeLa cells at 24 h was calculated on the concentration-response curve and was found to be 80.15% of DeflaGyn®. Increasing DeflaGyn® concentrations (12.5–100%) increased iROS (intracellular reactive oxygen species) levels 1.3-fold on average compared to the control (0.1% DMSO (dimethyl sulfoxide)). DNA damage and apoptosis levels increased significantly with concentration in a dose-dependent manner. Similarly, a decrease was observed in the mitochondrial membrane potential (MMP levels decreased statistically significantly up to 70.14%) and intracellular glutathione levels, and all changes were proportional to the dose. Although it is known that the combination of vaginal gel facilitates the regression of cervical dysplasia and clearance of high-risk HPV (Human Papilloma Virus) types, there is no detailed information on the mechanism by which it provides these effects. In the present study, we found that the specific vaginal gel had a dose-dependent effect on various parameters thought to be important in the process of cervical carcinogenesis. Further studies are needed to reveal the pathways through which the gel is effective and whether it has similar effects in vivo. [ABSTRACT FROM AUTHOR]

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs. [ABSTRACT FROM AUTHOR]

Current research aims to screen the anticancer prospective of Leucas biflora phytocompounds against apoptotic regulator target protein essential for cancer progression. In gas chromatography–mass spectrometry analysis major phytocompounds such as tetracosahexaene, squalene, phytol, 22‐stigmasten‐3‐one, stigmasterol, fluorene, and 1,4‐dihydro were identified in ethanolic leaf extract of Leucas biflora. In vitro, the free radical scavenging potential of ethanolic leaf extract of Leucas biflora was examined through its DPPH and ABTS radical scavenging potential IC50 value 15.35 and 13.20 μg/ml, respectively. Dose‐dependent cytotoxicity was monitored against both A549 lung cancer and HELA cervical cancer cells. Leucas biflora ethanolic leaf extract highly reduces the cell viability of both HELA and A549 cells in in vitro cytotoxicity assays. Leucas biflora ethanolic extract produces 23.76% and 29.76% viability rates against A549 lung and HELA cervical cancer cell lines, and their IC50 values differ slightly at 95.80 and 90.40 μg/ml, respectively. In molecular docking analysis lung cancer target protein–ligand complex 5Y9T‐16132746 showed a maximum score of −14 kcal/mol by exhibiting stable binding affinity and interactions among all screened complexes. Based on docking score nine phytocompounds from Leucas biflora and two reference standard drugs were chosen for further analysis. Further validation reveals that the fluorene, 1,4‐dihydro possess good ADMET, Bioactivity and density functional theory indices. [ABSTRACT FROM AUTHOR]

Gender stereotypes constructed by society are detrimental for women. Women were seen as weak and underestimated by society (the PEW Research Center’s survey in 2017). This study aims to discover how a film entitled Thor: Ragnarok (2017) countered gender stereotypes through the portrayal of the main female character, Hela, and to reveal the reason behind such portrayal of Hela. This study is a qualitative study because the data are qualitative data. The data of this study are clauses collected from the movie subtitles, containing Hela’s power to counter gender stereotypes. This study applied Fairclough’s Critical Discourse Analysis (three-dimensional framework), supported by Halliday’s Systemic Functional Linguistics (SFL), which focused on the transitivity system for the first-dimension analysis. After doing the three-dimensional analysis, it is found that Hela’s character in the movie is portrayed as opposing gender stereotypes. Hela is represented as strong, brave, and feared. These traits are against the stereotype of women described as weak, fearful, and underestimated. The reason behind the portrayal of Hela as a strong woman is to promote the feminism spirit to the people in that women should be empowered, in line with the goal of the United Nations (UN) Women and the UN Foundation that protect women's rights and supports women in achieving gender equality.

The use of mesenchymal stem cells (MSCs) for the treatment of various diseases is being investigated, however, their use in cervical cancer has not been well-studied. Here, we examined the impact of collected MSC–conditioned medium (CM) on 1 to 5 days on apoptosis, proliferation, and cytokine production of peripheral blood mononuclear cells (PBMCs) when co-cultured alongside the HeLa cell line for 24, 48, and 72 h by CFSE assay, flow cytometry, and real-time PCR, respectively. We found that CMs collected on the third day of MSCs culture significantly increased the proliferation of PBMCs and decreased the proliferation of HeLa cells after 48 h. CMs showed no significant effects on cell death, whereas it significantly increased the apoptosis of HeLa cells. Real-time PCR analysis showed that the presence of CM collected on the third day of MSCs culture caused a significant increase in the gene expression of IL2, IFN-γ, and TGF-β in PBMCs after 48 h co-culture with HeLa cells. The data mentioned earlier demonstrate that MSC–CM can induce the growth and endurance of PBMCs while concurrently culturing HeLa cells. This observation indicates their promising potential as immunomodulatory therapies for cervical cancer cells. Nevertheless, additional investigation is imperative to comprehensively comprehend the fundamental mechanisms and refine therapeutic strategies involving PBMCs and mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Mammalian cell lines devoid of mitochondrial DNA (mtDNA) are indispensable in studies aimed at elucidating the contribution of mtDNA to various cellular processes or interactions between nuclear and mitochondrial genomes. However, the repertoire of tools for generating such cells (also known as rho-0 or ρ0 cells) remains limited, and approaches remain time- and labor-intensive, ultimately limiting their availability. Ethidium bromide (EtBr), which is most commonly used to induce mtDNA loss in mammalian cells, is cytostatic and mutagenic as it affects both nuclear and mitochondrial genomes. Therefore, there is growing interest in new tools for generating ρ0 cell lines. Here, we examined the utility of 2′,3′-dideoxycytidine (ddC, zalcitabine) alone or in combination with EtBr for generating ρ0 cell lines of mouse and human origin as well as inducing the ρ0 state in mouse/human somatic cell hybrids. We report that ddC is superior to EtBr in both immortalized mouse fibroblasts and human 143B cells. Also, unlike EtBr, ddC exhibits no cytostatic effects at the highest concentration tested (200 μM), making it more suitable for general use. We conclude that ddC is a promising new tool for generating mammalian ρ0 cell lines.

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative - loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21 -loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21 -loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21 -loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21 -loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release. [ABSTRACT FROM AUTHOR]

In this work, we describe the synthesis and characterisation of the starting materials [Cp*IrCl2]2 and four new ruthenium(II) and iridium(III) complexes half sandwich, contain the fragments [(p-cymene)Ru]2+ and [Cp*Ir]2+; (Cp* = CpMe4Et) of stoichiometry: [Cp*IrCl2(2-aminopyridine)] (I), [Cp*IrCl2(4-aminopyridine)] (II), [Cp*IrCl2(adenine)] (III) and [(p-cymene)RuCl2(adenine)] (IV). The new compounds have been characterised by C, H, and N elemental analysis; infrared and 1H NMR spectroscopy with 1H–1H COSY, ESI/TOF mass spectrometry and thermogravimetry. A study of the cytotoxicity of these compounds against the Hela cell line was carried out, with results indicating a low activity. [ABSTRACT FROM AUTHOR]

L-glutaminase (L-glutamine aminohydrolase EC 3.5.1.2) is an extracellular hydrolytic enzyme having anticarcinogenic potential and is widely used in enzyme therapy especially for acute lymphocytic leukemia. L-glutaminase deaminates L-glutamine to glutamic acid and ammonia. In most tumors glutamine is the primary mitochondrial substrate and is present in circulating blood. It is a source of essential amino acid necessary for development of leukemic cells. The lack or depletion of L-glutamine leads to death of tumour cells. The marine environment is a potential source of bioactive secondary metabolites that provides pharmaceutically important compounds. The present study was focussed on to study the anticancer property of L-glutaminase producing actinomycetes isolated from estuaries of Uttara Kannada district of Karnataka. The isolates were screened for L-glutaminase production by qualitative and quantitative assay and the potent isolate was further subjected for MTT assay to determine its anticancer potential. The study showed 60% of isolates were positive for L-glutaminase production in Rapid plate assay and 85% of isolates were positive in semiquantitative assay. In quantitative assay the isolate Streptomyces albogriseolus exhibited high enzyme activity of 24.32+0.02 IU/ml. In MTT assay the isolate Streptomyces albogriseolus showed an IC50 value 102.0μg/ml in cervical cancer HeLa cells and IC50 value of 101.2μg/ml in HePG2 cells respectively, and could be used as good source of L-glutaminase. [ABSTRACT FROM AUTHOR]

Thermal gradients have emerged as a promising technique for manipulating and sorting biological material at the microscale, holding considerable potential in lab-on-a-chip technology. Herein, we propose a non-invasive thermohydrodynamic approach for fast cell manipulation using a microfluidic open-to-air device. Cell discrimination is achieved by simply changing the temperature gradient toward the control of the convective effect on their displacement. First, the size and morphology/roughness-based motion capabilities were modeled using polystyrene (PS) microparticles with different sizes (5 and 20 μm) and polycaprolactone (PCL) microspheres, respectively. Computational fluid dynamics simulations of the generated flow were also carried out to demonstrate the influence of both the thermohydrodynamic and Marangoni effects in the PS particle displacement, where the thermally induced convective effect was not enough to move the microparticles inside the channel, but the combination of thermally induced convection together with the Marangoni effect. Indeed, small particles (5 μm) followed a full convective path, whereas the bigger ones (20 μm) exhibited a rolling motion on the substrate from the cold side to the hot side. Also, the relationship between in-flow speed and PCL (≈ 20 μm) surface roughness confirmed the driving force of this convection-based approach. Then, the microfluidic device was successfully used to separate Henrietta Lacks cancer cells (HeLa) from red blood (RBCs) and fibroblast (HFF-1) cells. To this end, thermal gradients were tailored to achieve the desired thermohydrodynamic effect, showing a highly versatile performance. Both cell models (HeLa-RBCs and HeLa-HFF-1), due to rationale tweaking of the imposed temperature gradients (ΔT = 10 K, 303–293 K, and ΔT = 5 K, 303–298 K), were efficiently separated in less than 5 and 60 s, respectively; with excellent cell viabilities. The proposed microfluidic approach holds considerable promise for thermohydrodynamic sorting and manipulation of biological material by non-invasive methods using portable instrumentation. The potential parallelization of the thermal-convective approach opens new avenues for early disease diagnosis (liquid biopsies) or the study of biological systems, even at physiological temperatures with a potential impact in cell (organ)-on-a-chip technologies. [ABSTRACT FROM AUTHOR]

Plants have natural compounds which possess antiproliferative potential against many cancers. In the present study, Solanum nigrum was evaluated for its anti-cancerous properties. Different compounds have been documented in literature for having significant anti-tumor and anti-cancerous activities because of the presence of biologically active compounds. Current study aimed to isolate, characterize bioactive fractions and their antiproliferative potential in human cancer cell lines. Bioactive fraction (ethyl acetate) was subjected to column chromatography for the isolation and purification of compounds responsible for cytotoxic effect followed by thin layer chromatography. NMR was performed for the identification and characterization of bioactive (SN2 and SN3) compounds. The docking analysis was performed to study the interactions of isolated compounds as a ligand with three receptors with specifically allocated PDB IDs 3NUB, 1JUH and 1F16 respectively. Two compounds (SN2 and SN3) were purified through chromatography and evaluated for antiproliferative activity. Both SN2 (Quercetin) and SN3 (Chlorogenic acid) have demonstrated anticancer activity against HepG2 cell with IC 50 value of 13.15 μg/ml and 23.63 μg/ml respectively and against HeLa cell with IC 50 value of 12.95 μg/ml and 25.50 μg/ml respectively. The results demonstrated that pure compounds isolated from S. nigrum plant exhibited anticancer activity in liver and cervical cancer cell lines along with non-toxic effect on normal cells. [Display omitted] • Bioactive compounds i.e. chlorogenic acid and Quercetin were isolated, characterized from S. nigrum. • Chlorogenic acid and Quercetin show promising cytotoxicity in human cancer cell lines. • In silico studies displayed strong binding affinity of bioactive compounds to cancer receptors. [ABSTRACT FROM AUTHOR]

In Ayurveda, Cassia fistula L. commonly known as Aragvadha (disease killer) is highly valuable medicinal plant. In the present study, hexane fraction (CaMH), chloroform fraction (CaMC), ethyl acetate fraction (CaME) and methanol fraction (CaMM) isolated from C. fistula bark were explored for their cytotoxic potential against cervical carcinoma (HeLa), breast carcinoma (MCF-7) and osteosarcoma (MG-63) cell lines using MTT assay. Our results unveiled that C. fistula bark fractions were selectively cytotoxic to carcinoma cells and among the tested fractions CaMC fraction had highest selectivity index (SI) with a value of 9.77 in HeLa cells. CaMC fraction actuated apoptosis in HeLa cells, as evident from chromatin condensation, DNA fragmentation, externalization of phosphatidylserine, altered mitochondrial membrane potential and ROS generation. Moreover, CaMC fraction upregulated the expression of GSK3β and p53 which modulated the Bax/ Bcl-2 ratio and initiated the release of cytochrome c from mitochondria. The expression of caspase 3/9 was also found to be upregulated which ultimately induced apoptosis. We also found that CaMC induced cell cycle arrest at G 0 /G 1 phase and significantly inhibited the migration in HeLa cells. GC–MS analysis showed Oleic Acid, Piperine, Isopiperine and Tris(2,4-di‑tert-butylphenyl) phosphate as major constituents which could be attributed to anticancer activity of CaMC. The present study affirms the potential of CaMC fraction in modulating the aberrant signaling pathway for the induction of apoptosis in HeLa cells. [Display omitted] • CaMC fraction of cassia fistula L. bark possessed highest selective cytotoxicity against HeLa cells. • CaMC fraction altered mitochondrial membrane potential and increased ROS generation in HeLa cells. • CaMC fraction modulate the apoptotic events and induced intrinsic apoptotic death in HeLa cells. • GC–MS analysis revealed the presence of piperine and oleic acid as a major constituents of CaMC fraction. [ABSTRACT FROM AUTHOR]

Several reports have shown the antitumor activity of yellow passion fruit (YPF) (Passiflora edulis f. flavicarpa), but limited studies are exploring its mechanism. This study aimed to examine the antitumor mechanism of YPF juice on T47D and HeLa cell lines. The YPF juice was administered at doses of 0.25 IC50, 0.5 IC50, and IC50. The cytotoxic mechanism of YPF juice was determined by assessing the antiproliferative effects and apoptosis induction. The antiproliferative effects were assessed based on doubling time with MTT assay, while apoptosis induction and cell cycle were examined using flow cytometry with annexin-V and propidium iodide staining. The results showed that the doubling time of T47D and HeLa cells treated with YPF juice was longer than control cells. There was an increase significantly in the average number of apoptosis of T47D and HeLa cells treated with YPF juice. At a dose equivalent to IC50, the HeLa cell cycle was inhibited, leading to a 13% reduction in the G0-G1 phase. Whereas in T47D cells, almost all cells were in the sub-G0 phase, indicating cell cycle arrest across all phases. The results proved that YPF juice inhibited the cell cycle and increased apoptosis of T47D breast cancer cells and HeLa cervical cancer cells. [ABSTRACT FROM AUTHOR]

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Four triterpenoids, known as dammarane-type, dammaradienone (1), 20(S),25-epoxy-5α-dammar-20-en-3-one (2), 20(S)-5α-dammar-24-en-3α,20-diol-3-acetate (3) and 3α-acetyl-20S,24S-epoxy-25-hydroxydammarane (4), were isolated from Aglaia cucullata peel fruit. The structures of isolated compounds were identified based on their HR-TOFMS data and extensive NMR spectroscopic analysis, as well as compared with literature data. Compounds 1-4 were assessed for cytotoxic effects against HeLa cervical and B16-F10 melanoma skin cancer cells. All compounds showed moderate to weak activity against B16-F10 cancer cells, while compound 2 exhibited the strongest activity against HeLa cancer cells with IC50 of 7.10 µg/mL indicating that the existence of an epoxy moiety at the side chain increases the cytotoxicity to HeLa cells.

We investigated the invasion of Acinetobacter baumannii strains to epithelial cells and elucidated the role of antibodies against outer membrane protein A (OmpA). A. baumannii ATCC 19606 and clinical isolate 58ST were utilized. OmpA was expressed, purified, and administered to BALB/c mice, inducing anti-OmpA antibodies. OmpA cytotoxicity was evaluated. Two A. baumannii strains were selected to infect human cervical HeLa cells. Serum resistance was determined at sera dilutions. Adhesion, internalization, and proliferation of live and killed A. baumannii in HeLa cells were examined with and without anti-OmpA sera. HeLa cell viability was assessed with and without exposure of live A. baumannii strains to anti-OmpA sera. Cytoskeleton inhibitor experiments were conducted on epithelial cells to probe microfilament and microtubule involvement in A. baumannii invasion. OmpA prompted antibody production without toxicity in mice. A. baumannii strains displayed varying cell invasion abilities, notably the clinical strain exhibiting the highest invasion. A. baumannii cells localized within vacuoles during internalization, migrating towards the nucleus, using a zipper-like invasion process. Bacterial proliferation within host cells led to HeLa cell death. Pre-treatment with anti-OmpA antibodies significantly curbed adhesion and invasion of A. baumannii in HeLa cells. Microscopic imaging provided proof of the intracellular presence of A. baumannii in HeLa cells. In conclusion, the OmpA plays a crucial part in A. baumannii - epithelial cell interactions. The results add to our knowledge of pathogenesis during the initial stages of infection by A. baumannii.

Background: Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) and the small GTPase protein Ras-related protein Rab-22 A (RAB22A) may be colocalized in the cytoplasm and that as a conequence they may enhance the formation of microvesicles in breast cancer cells under hypoxia. Therefore, we sought to determine whether these two proteins are present in intracellular complexes in breast carcinoma cells. Methods and results: Evaluation using molecular docking indicated that HIF-1α and RAB22A interact with each other. Co-immunoprecipitation of endogenous or ectopically expressed HIF-1α and RAB22A proteins in MDA-MB-231 breast cancer cells or HEK-293T cells demonstrated that endogenous HIF-1α and RAB22A can form an intracellular complex; however, transiently expressed HIF-1α and RAB22A failed to interact. Investigating RAB22A and HIF-1α interactions in various cancer cell lines under hypoxia may shed light on their roles in cancer cell survival and progression through regulation of intracellular trafficking by HIF-1α under hypoxic conditions. Conclusions: Our study is the first to reveal the potential involvement of HIF-1α in intracellular trafficking through physical interactions with the small GTPase protein RAB22A. We discuss the implications of our work on the role of exosomes and microvesicles in tumor invasiveness. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer, the most common reproductive system cancer being women, is the fourth leading cause of cancer-related deaths. The use of mesenchymal stem cells (MSCs) for treating various diseases is being studied, but their use in cervical cancer has not been well explored. In this study we study investigated the effect of adipose tissue-derived MSCs on the apoptosis and proliferation of peripheral blood mononuclear cells (PBMCs) in co-culture with the HeLa cell line. MSCs were isolated from adipose tissue and then co-cultured with PBMCs, and HeLa cells at different time points (24, 48, and 72 hours). Materials and Methods: The effect of MSC cells on proliferation, apoptosis, and gene expression of the cytokines tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin (IL)-4, IL-2, and interferon-γ in PBMCs cultured together with HeLa cells was investigated using flow cytometry and real-time polymerase chain reaction (PCR), respectively. Results: Flow cytometry showed that co-culture of PBMCs/MSCs/HeLa significantly increased the proliferation of PBMCs at different time points, with a p-value of 0.0022. In addition, MSCs significantly decreased apoptosis of PBMCs in co-culture with HeLa at 48 h. the p-value was 0.0022. Real-time PCR showed that the expression of TGF-β in PBMCs/MSCs/HeLa co-culture increased after 24 h, with a p-value of 0.006. Conclusion: These data showed that adipose-derived MSCs can stimulate the proliferation and survival of PBMCs and enhance the apoptosis of HeLa cells, indicating their potential as immunomodulatory therapy for cervical cancer cells. However, further research is required to fully understand the underlying mechanisms and optimize therapeutic approaches involving PBMCs and MSCs. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor‐α (TNF‐α) is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF‐α‐modulated epitranscriptomic m6A marks is unknown. We employed a genomewide approach to examine the extent of m6A RNA modifications under TNF‐α‐modulated apoptotic conditions in HeLa cells. miCLIP‐seq analyses revealed a plethora of m6A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m6A RNA modification patterns were quite different under cisplatin‐ and TNF‐α‐mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF‐α treatment conditions. Our analyses showed changes in the translational efficiency of TP53INP1 mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF‐α treatment but not CP treatment, suggesting the existence of a pathway‐specific METTL3‐TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF‐α‐mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway‐specific m6A methylation marks exist in cells and TNF‐α‐METTL3‐TP53INP1 axis modulates TNF‐α‐mediated apoptosis in HeLa cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The human papillomavirus (HPV), a major carcinogenic pathogen, can cause cervical cancer through persistent infection. The immune system typically fights off the virus, albeit long-term activation may promote carcinogenesis. The micro-immunotherapy medicine 2LPAPI® holds promise for aiding viral clearance and mitigating cervical cancer risk, and our research aimed to examine the effects of this medicine in vitro. We focused our investigations on the two most prevalent genotypes of HPV causing persistent infection, HPV-16 and HPV-18. We found that 2LPAPI® boosted the secretion of IL-6, IFN-γ, and IP-10 in human immune cells when exposed to HPV-16 proteins, suggesting enhanced defensive responses to HPV-16. Some of the active substances curtailed T-cell proliferation and activity and displayed antiproliferative properties on HPV-18 positive cervical cancer-derived HeLa cells in nutrient-restricted conditions. These results unveil 2LPAPI®'s potential dual role: immunomodulation for HPV-16-affected immune cells and antiproliferative activity against a model of HPV-18-positive-cervical cancer cells. Human papillomavirus (HPV) is the second most common infectious agent causing cancer. Persistent infection with high-risk (HR)-HPV can lead to cervical intra-epithelial neoplasia and cervical carcinomas (CC). While host immune response is necessary for viral clearance, chronic immune activation contributes to a low-grade inflammation that can ultimately lead to carcinogenesis. The micro-immunotherapy medicine (MIM) 2LPAPI® could be a valuable tool to manage the clearance of the virus and reduce the risk of developing CC. In this in vitro study, we aimed to investigate its mode of action. We showed that actives from the MIM increased the IL-6, IFN-γ, and IP-10 secretion in human peripheral blood mononuclear cells (PBMCs) exposed to peptides derived from the HPV-16 capsid (HPV16(L1)). This could reflect an increase in the immune activity toward HPV-16. At the same time, some active substances reduced the lympho-proliferation and the expression of T-cell activation markers. Finally, some of the MIM actives displayed antiproliferative effects in CC-derived HeLa cells under serum-starvation conditions. Altogether, this body of data highlighted for the first time the dual effect of MIM in the framework of HR-HPV infections as a potential (i) immune modulator of HPV16(L1)-treated PBMCs and (ii) antiproliferative agent of HPV-positive CC cells. [ABSTRACT FROM AUTHOR]

Allicin is a safe herbal extract believed to have antitumor effects, which, however, remain unclear. The aim of the present work was to discuss Allicin antitumor effects on cervical cancer using cell experiments. Using Hela and Siha to our research objectives in our study, first step, difference concentration of Allicin (20, 40, and 80 μM) treated Hela and Siha cell lines, and next step, discuss circEIF4G2 effects in Allicin antitumor effects in Hela and Siha cell lines; the cell proliferation and EdU‐positive cell number by CCK‐8 and EdU staining; cell apoptosis rate by flow cytometry; invasion cell number by transwell assay; wound healing rate by wound healing assay; and relative mRNA and protein levels using qRT‐PCR and WB assay. With Allicin supplement, the cell proliferation and EdU‐positive cell number were significantly depressed with cell apoptosis rate significantly increasing; invasion cell number and wound healing rate significantly suppressed with circEIF4G2 mRNA expression significantly down‐regulation (p <.05, respectively). However, there was no significant difference among Allicin, si‐circEIF4G2, and Allicin+si‐circEIF4G2 in cell biological activities including cell proliferation, apoptosis, invasion and migration, and relative gene and protein expression. Allicin depresses biological activities of cervical cancer cells through down‐regulating circEIF4G2/HOXA1/AKT/mTOR. [ABSTRACT FROM AUTHOR]

Consistent human papillomavirus infection is the primary cause of uterine cervical cancer (HPV). There is a need for a more suitable and efficient treatment method due to the negative side effects of conventional chemotherapeutics used to treat advanced metatstatic cervical cancer. Recent research has shown that plant Cimicifuga racemosa (family Ranunculaceae) has powerful anti-inflammatory, antioxidant effects and anticancer effects. However, its potential against cervical cancer has not yet been clarified. Therefore, this work was aimed to examine the antiproliferative and cytotxic effects of Cimicifuga racemosa rhizome extract on human cervical cancer cells. Our results showed a dose-dependent growth inhibition in cervical cancer HeLa cells when treated with various doses of ethyl acetate rhizome extract of C. racemosa. Morpholigical analysis showed marked alterations in cancer cells including shrinking, blebbing and rounding. In addition, marked nuclear alterations in HeLa cells were observed by Hoechst 33342 staining. The H2DCFDA staining showed increased production of reactive oxygen species (ROS). Significant reduction in mitochondrial membrane potential was also observed in HeLa cells by Rhodamine123 staining. Thus the results of the study signifies the effectiveness of C. racemosa rhizome extract in cervical cancer cells, suggesting its importance as a source of potential anticancer agents for further in vitro and in vivo evaluation. [ABSTRACT FROM AUTHOR]

We present novel workflows for Q-FISH nanoscopy with the potential for prognostic applications and resolving novel chromatin compaction changes. DNA-fluorescence in situ hybridization (DNA-FISH) is a routine application to visualize telomeres, repetitive terminal DNA sequences, in cells and tissues. Telomere attrition is associated with inherited and acquired diseases, including cancer and cardiomyopathies, and is frequently analyzed by quantitative (Q)-FISH microscopy. Recently, nanoscopic imaging techniques have resolved individual telomere dimensions and their compaction as a prognostic marker, in part leading to conflicting conclusions still unresolved to date. Here, we developed a comprehensive Q-FISH nanoscopy workflow to assess telomeres with PNA telomere probes and 3D-Stimulated Emission Depletion (STED) microscopy combined with Dynamic Intensity Minimum (DyMIN) scanning. We achieved single-telomere resolution at high, unprecedented telomere coverage. Importantly, our approach revealed a decrease in telomere signal density during mitotic cell division compared to interphase. Innovatively expanding FISH-STED applications, we conducted double FISH targeting of both telomere- and chromosome-specific sub-telomeric regions and accomplished FISH-STED in human cardiac biopsies. In summary, this work further advanced Q-FISH nanoscopy, detected a new aspect of telomere compaction related to the cell cycle, and laid the groundwork for future applications in complex cell types such as post-mitotic neurons and muscle cells. [ABSTRACT FROM AUTHOR]

The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic areas of Africa as of December 2023. In this article, we analyze the sequences of full genomes of Mpox virus from Europe and compare them with all available Mpox sequences of historical relevance, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Mpox, with >99 % sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins between the current outbreak, previous Mpox and Cowpox sequences, and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other Mpox/Cowpox/Variola viruses shows a very high conservation, with 97.9 % (protein-based) and 97.8 % (nucleotide-based) sequence identity. We identified significant correlation in human transcriptional responses as well, with a conserved immune pathway response induced in human cell cultures by the three families of Pox virus. The similarities identified between the major strains of Pox viruses, as well as within the Mpox clades, both at the genomic and transcriptomic levels, provide a molecular basis for the observed efficacy of Variola vaccines in other Poxviruses. [ABSTRACT FROM AUTHOR]

The green synthesis method used to synthesize Co3O4-NPs has attracted numerous advantages due to its low cost, less time and energy consume, no need of special instruments for experimental and more eco-friendly with environment. In this study, the Co3O4-NPs were synthesized by green synthesis method to overcome the toxicity of chemical synthesis. And Allium tuncelianum plant which is an endemic species in Tunceli was used as a reducing agent and Co(NO3)2.6H2O as a source of cobalt. The synthesized Co3O4-NPs were characterized by using FTIR, XRD, SEM and HR-TEM techniques. The XRD pattern was shown that the Co-NPs were face-centered cubic (fcc) of crystalline nature and the average crystallite size was found nearly 23 nm with a value of COD(R^2): 0.982. The Co3O4-NPs generally had a spherical shape in the SEM images taken at 200 nm. The Co3O4-NPs showed low IC50 value against HeLa cells compare with RPE normal cells. [ABSTRACT FROM AUTHOR]

In order to evaluate the role of substituents at 3-C and 17-C in the cytotoxic and cytoprotective actions of DHEA and 5-AED molecules, their derivatives were synthesized by esterification using the corresponding acid anhydrides or acid chlorides. As a result, seven compounds were obtained: four DHEA derivatives (DHEA 3-propionate, DHEA 3-butanoate, DHEA 3-acetate, DHEA 3-methylsulfonate) and three 5-AED derivatives (5-AED 3-butanoate, 5-AED 3,17-dipropionate, 5-AED 3,17-dibutanoate). All of these compounds showed micromolar cytotoxic activity toward HeLa and K562 human cancer cells. The maximum cytostatic effect during long-term incubation for five days with HeLa and K562 cells was demonstrated by the propionic esters of the steroids: DHEA 3-propionate and 5-AED 3,17-dipropionate. These compounds stimulated the growth of normal Wi-38 cells by 30–50%, which indicates their cytoprotective properties toward noncancerous cells. The synthesized steroid derivatives exhibited antioxidant activity by reducing the production of reactive oxygen species (ROS) by peripheral blood mononuclear cells from healthy volunteers, as demonstrated in a luminol-stimulated chemiluminescence assay. The highest antioxidant effects were shown for the propionate ester of the steroid DHEA. DHEA 3-propionate inhibited luminol-stimulated chemiluminescence by 73% compared to the control, DHEA, which inhibited it only by 15%. These data show the promise of propionic substituents at 3-C and 17-C in steroid molecules for the creation of immunostimulatory and cytoprotective substances with antioxidant properties. [ABSTRACT FROM AUTHOR]

Sesquiterpenoids belong to a group of terpenoid compounds with interesting structures that are abundant in natural products especially in higher plants. Sesquiterpenoids have a wide variety of bioactivities with great potential cytotoxic activity. The species Dysoxylum excelsum belongs to the Meliaceae family known as higher plant, but only a few sesquiterpenoids have been reported particularly for their cytotoxic activity. Therefore, this research aims to isolate and elucidate the sesquiterpenoids structure from D. excelsum stem bark and examines their cytotoxicity against HeLa cervical cancer cells. Through various column chromatography separations, four known sesquiterpenes namely β-caryophyllene oxide (1), caryophyllenol II (2), humulene dioxide A (3), and guai-6-en-10β-ol (4) were acquired from the n-hexane extract. Compounds 1-4 were isolated for the first time from D. excelsum species. The sesquiterpenoid structures were elucidated according to Nuclear Magnetic Resonance, Infrared, and HR-TOF-MS analysis. The cytotoxicity compounds 1-4 was determined against HeLa cervical cancer cells by examination with the PrestoBlue method and compound 3 exhibited the most potent cytotoxicity with an IC50 value of 160.74 μM. [ABSTRACT FROM AUTHOR]

Grewia bracteata Roth stem was investigated for its anticancer potential for the first time. Initially, polarity-guided extracts from three solvents were screened on HeLa, HCT- 116 and MCF-7 tumours cells. The results revealed that ethyl acetate extract (GSE) significantly (p < 0.05) inhibited HeLa, HCT- 116 and MCF-7 cells with respective IC50 values of 30.58, 14.26 and 22.91 µg/mL. GSE inhibited HCT-116 cells with 6- and 21-folds higher than hexane (GSN) and methanol (GSM) extracts, respectively. Hence, column chromatography of GSE was performed and fractionated to 18 fractions. The obtained fractions were further tested on HCT-116 cells. Amongst, the fractions HF6 and DF1 were active with the respective IC50 values of 25.35 and 31.28, µg/mL (p < 0.05). These active fractions were profiled using H1-NMR, C13-NMR and LC-MS/MS analysis, and found the presence of pentacyclic triterpenoids like betulin diacetate and ursolic acid. [ABSTRACT FROM AUTHOR]

Cervical cancer is known as the second most pervasive malignancy in women across the globe. The role played by microRNAs (miRNAs) in the initiation, progression, and metastasis of this cancer has received specific attention. The use of natural compounds leading cancer cells toward apoptosis is a feasible strategy for cancer therapy. Oleuropein, an olive‐extracted phenolic substance, displays anticancer properties. Here, it was attempted to assess the role played by oleuropein in cell viability in cervical cancer and changes in the expression of some miRNAs associated with cervical cancer as well as some of their possible target genes selected using bioinformatics analysis. For this purpose, HeLa cell line was exposed to several oleuropein concentrations for 48 and 72 h. After that, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay and flow cytometry were employed to assess cell viability and apoptosis, respectively. In addition, to conduct bioinformatics analysis, Cytoscape computer program was used based on STRING database. Furthermore, to examine the role played by oleuropein in the expression of miRNAs of interest as well as their potential target genes, real‐time PCR was employed. The findings indicated that oleuropein reduced cell viability through inducing apoptosis. As a result of treatment with oleuropein, miR‐34a, miR‐125b, and miR‐29a showed increased expression levels, whereas miR‐181b, miR‐221, and miR‐16 showed decreased expression levels. Furthermore, oleuropein reduced the expression of the anti‐apoptotic genes Bcl‐2 and Mcl1, whereas it elevated the expression of the pro‐apoptotic Bid, Fas, and TNFRSF10B genes and the p53 tumor suppressor. Our results indicate that the apoptosis induction is a mechanism of action of oleuropein in HeLa cells. Because of its effect on the reflation of the expression of genes and miRNAs effective in the pathogenesis of cervical cancer, oleuropein shows potential as an effective research tool for developing new natural drugs for treating cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Artemisia deserti Krasch belongs to Asteraceae family, and has many medicinal properties that used to treat a variety of diseases, including antihypertensive, invigorating blood circulation, antiallergy, antiviral, antitumor, and antioxidant. Methods: The objective of this study was the evaluation of cytotoxic and antioxidant activities as well as the chemical composition of A. deserti essential oil extracted by different extraction methods. These extraction methods included hydro-distillation (HD), salt-HD (Salt pretreatment followed by HD), maceration-HD (maceration pretreatment followed by HD), acid-HD (acid pretreatment followed by HD), ultrasound-HD (ultrasound pretreatment followed by HD), and enzyme-HD (enzyme pretreatment followed by HD). Results: The results revealed that the highest yield of essential oil was achieved by acid-HD (0.48% ± 0.11%). In all methods, the main compounds of essential oil were camphor (44.32%–66.80%), piperiton (14.11%–24.33%), and 1,8-cineole (4.85%–6.75%). The antioxidant property of essential oils was investigated using the DPPH method. Based on the results, the essential oils extracted by acid-HD and enzyme-HD methods had the highest property. The cytotoxic property of A. deserti essential oils was evaluated. The results demonstrated that the essential oil extracted by enzyme-HD indicated the highest cytotoxicity activity against human cervical carcinoma (HeLa) cells in both 24 and 48 h. Based on the gas chromatography-mass spectrometry results, 1,8-cineol, carvacrol, thymol, and myristicin were rich in the essential oil extracted by enzyme-HD, and the highest cytotoxicity activity of essential oil obtained by enzyme-HD method is probably related to these compounds. Conclusion: In addition, it was observed that enzyme-HD is an effective method in the extraction of essential oil with the highest antioxidant and cytotoxic activities.

The reaction of the synthesized (E)‐1‐(4‐((2,4‐dihydroxy‐6‐methylphenyl)diazenyl)phenyl)ethan‐1‐one, (DMPDE) ligand with Ag(I) ion at room temperature resulted in the formation of the complex; [Ag(DMPDE)(H2O)2]. 1H NMR, 13C NMR, FTIR, UV‐Vis, mass spectra, elemental analyses, thermal analysis (TGA/DTA), and molar conductance measurements were done to elucidate the structure of synthetic compounds. The results revealed an interesting geometrical variation; tetrahedral for Ag(I) complex. FT‐IR spectra demonstrated that the ligand (DMPDE) under investigation behaves as a bidentate ligand (N,O) through the nitrogen atom of the azo group which is the farthest of the acetophenone moiety and oxygen phenolic for benzene moiety and forms a stable five‐membered chelating ring. The electronic structure, molecular electrostatic potential (MEP) and quantum chemical calculations of the newly synthesized compounds are investigated theoretically at the DFT/B3LYP level of theory. Additionally, the ligand (DMPDE) and Ag(I) complex were screened against the growth of pathogenic bacteria [Actinomycosis (G+), E. Escherichia Coli (G−)] and fungi (Penicillium spp.) compared with the reference antibiotics, Chloramphenicol and Nystatin. Furthermore, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) was used to evaluate the antioxidant activities of the ligand and its complex, which showed they both possess significant antioxidant properties in comparison with L‐ascorbic acid (Vit. C) as standard. Based on docking studies, (DMPDE) and Ag(I) complex demonstrated a greater affinity for (PDB ID: 3T88), which corresponds to Escherichia coli protein (−6.7818 kcal/mol) and (−6.7928 kcal/mol), respectively. Interestingly, the most active Ag(I) complex inside the active site of cervical cancer receptor (PDB ID: 4XR8) demonstrated a higher binding energy (−6.2631 kcal/mol) than free ligand (−5.8561 kcal/mol). In silico, ADMET displayed that compounds obey the Lipinski rule and the "Veber's rule. Consequently, is likely to exhibit oral bioavailability with good LD50 and a safety profile that includes non‐cytotoxicity, non‐immunotoxicity, and non‐skin sensitization. Finally, the compounds synthesized showed significant anticancer activity in human cervical cancer cell lines HeLa and SiHa compared with positive controls (cisplatin) and normal human hepatic cells (WRL‐68). In the present study, all tested cancer cell lines showed promising activity against Ag(I) complex, whose IC50 value ranged from (61.02 to 71.09) μg/mL. [ABSTRACT FROM AUTHOR]

The search for alternatives to cisplatin has led to the development of new metal complexes where thiazoline derivatives based on platinum(II) and palladium(II) stand out. In this sense, the Pt(II) and Pd(II) complexes coordinated with the thiazoline derivative ligand 2-(3,4-dichlorophenyl)imino-N-(2-thiazolin-2-yl)thiazolidine (TdTn), with formula [PtCl2(TdTn)] and [PdCl2(TdTn)], have previously shown good results against several cancer lines; however, in this work, we have managed to improve their activity by supporting them on mesoporous silica nanoparticles (MSN). The incorporation of metal compounds with a melatonin derivative (5-methoxytryptamine, 5MT), which is a well-known antioxidant and apoptosis inducer in different types of cancer, has been able to increase the cytotoxic activity of both MSN-supported and isolated complexes with only a very low amount (0.35% w/w) of this antioxidant. The covalently functionalized systems that have been synthesized are able to increase selectivity as well as accumulation in HeLa cells. The final materials containing the metal complexes and 5MT (MSN-5MT-PtTdTn and MSN-5MT-PdTdTn) required up to nine times less metal to achieve the same cytotoxic activity than their corresponding non-formulated counterparts did, thus reducing the potential side effects caused by the use of the free metal complexes. [ABSTRACT FROM AUTHOR]

Compounds Ro-714, Ro-716, and Ro-728 containing an antiestrogenic steroid moiety associated with a bis-β-chloroethylamine group exhibit pronounced antitumor activity in various animal models. Binding of antiestrogen-cytostatics to estrogen receptor subtypes having different functions has not been studied before. The binding affinity of Ro-714, Ro-716, and Ro-728 with estradiol receptor subtypes α and β (ERα and ERβ) was predicted using a molecular docking approach. The calculated binding affinity between the antiestrogen-cytostatics and ERα was comparable to that between ERα and tamoxifen, a drug widely prescribed to treat estrogen-dependent tumors. However, the calculated binding affinity between the antiestrogen-cytostatics and ERβ differed significantly from that of tamoxifen but was comparable to that of native ligands such as estradiol, estetrol, estriol, and estrone. It is assumed that the antitumor effects of Ro-714, Ro-716, and Ro-728 will depend on the ratio of ERα and ERβ subtypes in a malignant formation. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H2O2) and act as ROS scavenging systems, which are important for controlling the redox state of cells. Recently, cerium oxide nanoparticles were found to increase the water and H2O2 permeability by modulating AQPs. To further analyze the action of nanoparticles (NPs) on AQP, we examined the effect of the NPs presenting different core compositions (CeO2, Gd2O3, Fe3O4, and TiO2), hydrodynamic sizes, and surface functionalization. The NPs produced an increase in H2O and H2O2 permeability as a general trend. The hydrodynamic sizes of the NPs in the range of 22–100 nm did not produce any significant effect. The chemical nature of the NPs' core did not modify the effect and its intensity. On the other hand, the NPs' functionalized surface plays a major role in influencing both water and H2O2 permeability. The results suggest that NPs can play a significant role in controlling oxidative stress in cells and might represent an innovative approach in the treatment of a number of pathologies associated with an increased oxidative status. [ABSTRACT FROM AUTHOR]

The short‐tandem‐repeats (STR) profiles of MGc80‐3 and HeLa partially overlap, raising suspicion of contamination in the MGc80‐3 cell line. However, there has not been any relevant study demonstrating whether MGc80‐3 was fully replaced by HeLa cells, just mixed with HeLa cells (co‐existing), or was a somatic hybrid with HeLa cells. In addition to STR profiling, various approaches, including single nucleotide polymorphisms genotyping, polymerase chain reaction, screening for human papillomaviruses type 18 (HPV‐18) fragment, chromosome karyotyping, pathological examination of xenografts, tissue‐specific‐90‐gene expression signature and high‐throughput RNA sequencing were used to determine the nature of MGc80‐3. Our study found that the abnormal STR profile, partially overlapping with that of HeLa cells (64.62% to 71.64%), could not verify MGc80‐3 as a HeLa cell line. However, the STR 13.3 repeat allele in the D13S317 locus that seemed to be unique to HeLa cells was detected in MGc80‐3. Almost all the MGc80‐3 cells exhibited HPV‐18 fragments in the genome as well as certain HeLa marker chromosomes, such as M7 and M12. The molecular assay of the 90‐gene expression signature still considered MGc80‐3 as a stomach cancer using an algorithmic analysis. The expression pattern of multiple genes in MGc80‐3 was quite different from that in HeLa cells, which showed that certain characteristics belonged to gastric cancer cell lines. High throughput RNA sequencing showed the distinct patterns of gene expression in MGc80‐3. In conclusion, MGc80‐3 cell line is a somatic hybrid with HeLa cells rather than a pure gastric cancer cell line. [ABSTRACT FROM AUTHOR]

Background: Artemisia deserti Krasch belongs to Asteraceae family, and has many medicinal properties that used to treat a variety of diseases, including antihypertensive, invigorating blood circulation, antiallergy, antiviral, antitumor, and antioxidant. Methods: The objective of this study was the evaluation of cytotoxic and antioxidant activities as well as the chemical composition of A. deserti essential oil extracted by different extraction methods. These extraction methods included hydro-distillation (HD), salt-HD (Salt pretreatment followed by HD), maceration-HD (maceration pretreatment followed by HD), acid-HD (acid pretreatment followed by HD), ultrasound-HD (ultrasound pretreatment followed by HD), and enzyme-HD (enzyme pretreatment followed by HD). Results: The results revealed that the highest yield of essential oil was achieved by acid-HD (0.48% ± 0.11%). In all methods, the main compounds of essential oil were camphor (44.32%-66.80%), piperiton (14.11%--24.33%), and 1,8-cineole (4.85%-6.75%). The antioxidant property of essential oils was investigated using the DPPH method. Based on the results, the essential oils extracted by acid-HD and enzyme-HD methods had the highest property. The cytotoxic property of A. deserti essential oils was evaluated. The results demonstrated that the essential oil extracted by enzyme-HD indicated the highest cytotoxicity activity against human cervical carcinoma (HeLa) cells in both 24 and 48 h. Based on the gas chromatography-mass spectrometry results, 1,8-cineol, carvacrol, thymol, and myristicin were rich in the essential oil extracted by enzyme-HD, and the highest cytotoxicity activity of essential oil obtained by enzyme-HD method is probably related to these compounds. Conclusion: In addition, it was observed that enzyme-HD is an effective method in the extraction of essential oil with the highest antioxidant and cytotoxic activities. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is chemotherapy for breast and cervical cancer with serious side effects. Ketapang (Terminalia catappa) is a potential plant as a cochemotherapy agent. The purpose of this research was to examine the sensitivity of DOX as a cytotoxicity drug in combination with ethanolic extracts of ketapang leaves (EKL) against T47D and HeLa cancer cells. Cytotoxicity was determined using the MTT assay, with DOX concentration series (0.625-40 nM for T47D and 0.5-6 M for HeLa) and EKL (50-1000 g/mL) used in combination with the study. DOX and EKL combination assays utilizing their respective IC50 values were performed in T47D cells and HeLa cells, and the results were used to calculate the Combination Index (CI). Furthermore, the doubling time method was used to investigate the combination of DOX and EKL proliferation inhibition on both cell lines. DOX and EKL had IC50 values of 158 nM and 30 g/mL for T47D, respectively, and 3.4 M and 640 g/mL for HeLa cell growth. While DOX and EKL have a synergistic effect on T47D cells, their combined effect on HeLa cells is cytotoxic and dose-dependent. EKL increases the inhibitory effect of DOX on the proliferation of T47D and HeLa cancer cells. In T47D cells, the combination of DOX and EKL has a higher potential for cytotoxic and antiproliferative activity than in HeLa cells. [ABSTRACT FROM AUTHOR]

Background/Aim: Cervical cancer (CC) poses a significant threat to women's health and has a relatively poor prognosis due to local invasion and metastasis. It is, therefore, crucial to elucidate the molecular mechanisms of CC metastasis. SNHG3 has been implicated in various tumor metastasis processes, but its involvement in CC has not been thoroughly studied. Our study aimed to investigate the role of SNHG3 in metastasis and elucidate its underlying mechanisms in CC. Materials and Methods: LncRNA SNHG3 expression in CC tissues was analyzed using TCGA and GSE27469 databases. Normal cervical epithelial cells and CC cell lines were used to detect mRNA expression of SNHG3 via quantitative reverse transcription polymerase chain reaction (qRT-PCR). With RNA interference (RNAi) technology, antisense oligonucleotides (ASO) can act on HeLa cells to knockdown target gene expression. The influence of SNHG3 on cell migration and invasion were determined by wound healing and transwell assays. Transcriptome sequencing (RNA-seq) was used to seek abnormally expressed genes between SNHG3 knockdown cells and control cells. The expressions of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling related proteins were detected using western blot. Results: SNHG3 was obviously up-regulated in CC tissues and cell lines, and ectopic expression of SNHG3 was associated with lymph node metastasis of CC. Knockdown of SNHG3 significantly inhibited cell migration and invasion in CC. Further molecular mechanism studies showed that SNHG3 knockdown could down-regulate the expression of WNT1 Inducible Signaling Pathway Protein 2 (WISP2) so as to inhibit the activation of the Wnt/ß-catenin signaling pathway, and regulated the expression of EMT-related markers, that promoted the protein expression of E-cadherin, as well as decreased the expression of N-cadherin and vimentin. Conclusion: SNHG3 appears to exert a prometastatic effect in CC, as evidenced by inhibition of cell migration and invasion upon SNHG3 knockdown. EMT also appears to be attenuated. Of interest is the down-regulation of WISP2 following SNHG3 knockdown leads to the inactivation of the Wnt/ß-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cervical cancer is one of the most common types of frequently found cancers in Thailand. One of the causative agents is the infection of the high-risk human papillomavirus (HPV) type 16 and 18. Traditional medicines are rich sources of bioactive compounds which are a valuable source for the development of novel cancer therapies. In this study, the therapeutic effects of 3 traditional medicines, KerraTM, KSTM, and MinozaTM, were studied on HeLa and CaSki cells. Materials and Methods: The effects of KerraTM, KSTM, and MinozaTM on cancer cells were evaluated through cytotoxicity and cell death assays. The infection assay using HPV-16 pseudovirus was also carried out. Results: All traditional medicines efficiently suppressed cell growths of HeLa and CaSki, with KerraTM being the most potent anticancer agent followed by KSTM and MinozaTM. KerraTM at 158 µg/mL and 261 µg/mL significantly increases the percentage inhibition of the HPV-16 pseudovirus infection in a pre-attachment step in a dose-dependent manner, while KSTM at 261 µg/mL efficiently inhibited viral infection in both pre-attachment and adsorption steps. However, KerraTM, KSTM, and MinozaTM at subtoxic concentrations could not reduce the viral E6 mRNA expressions of HPV-16 and HPV-18. Cell death assay by acridine orange/ethidium bromide showed that KerraTM increased population of dead cells in dose-dependent manner in both CaSki and HeLa. The percentage of secondary necrosis in KerraTM-treated CaSki was higher than that of HeLa cells, while the percentage of late apoptotic cells in HeLa was higher than that of CaSki, indicating that HeLa was more susceptible to KerraTM than CaSki. For KSTM and MinozaTM, these extracts at 250 µg/mL promoted autophagy over cell death. At 500 µg/mL, the percentage of dead cells in KerraTM was higher than that of KSTM and MinozaTM. Conclusions: KerraTM is a potent traditional medicine for promoting cancer cell death. KerraTM is possibly useful in the prevention and treatment of cervical cancer. Further investigation will be carried out to gain a better understanding of the biochemical mechanism and the pharmacological activity underlying this effect. [ABSTRACT FROM AUTHOR]

In this investigation, the cytotoxic activity of phenazine compounds from different bacterial strains of Pseudomonas chlororaphis subsp. aurantiaca against the HeLa cervical adenocarcinoma cell line was studied. The cytotoxic concentrations of phenazines against HeLa cells were 300 μg/mL. After incubation with phenazines, cytological preparations of HeLa cells showing the presence of apoptotic bodies were obtained. The effect of phenazines on HeLa cells led to a change in the expression of their ABC transporter genes (abcc1 and abcg2) and tp53. The activity of tp53 increased almost 13-fold, while the expression of the abcc1 and abcg2 genes decreased. The activation of tp53 is one of the probable causes of apoptotic death of HeLa cells in the presence of phenazine compounds from the bacterium P. chlororaphis subsp. aurantiaca. [ABSTRACT FROM AUTHOR]

The goal of the study was a comparing the degree of development of autophagy in the human cervical carcinoma cells of HeLa-V and HeLa-R sublines and non-tumor human embryonic kidney cells HEK 293 under two types of starvation conditions—24- and 48-h culture in serum-free DMEM medium and 4-h incubation in Earle's minimal medium. The work assessed cell viability using MTT method and the expression of apoptosis (BCL2, BAX, CASP3) and autophagy (ULK1, BECN1, ATG5, ATG14, MAP1LC3B) genes using real-time PCR. Cultivation under serum starvation and in Earl's medium resulted in a significant decrease in the viability of HEK 293 cells, but had no influence on HeLa-V and HeLa-R cells. In the tumor cells of both lines, the expression of anti-apoptotic gene BCL2 increased, while in HEK 293 cells the BCL2/BAX ratio decreased and CASP3 gene was activated. In HeLa-V and HeLa-R cells, nutrient deprivation stimulated various combinations of genes ULK1, BECN1, ATG5 and ATG14 implicated in the initial stages of autophagy, but none of the treatments affected the expression of MAP1LC3B gene. In HEK 293 cells, serum starvation led to increase in expression level of BECN1, ATG5, ATG14 and MAP1LC3B genes. Thus, stimulation of autophagy in HeLa cells, especially HeLa-R, prevents the development of apoptosis, while in HEK 293 cells the processes of apoptosis and autophagy occur in parallel. Culture in the serum-free DMEM for 48 h appears to be most effective way to induce autophagy in tumor cell lines and, accordingly, the most suitable model for studying the role of autophagy in the development of their resistance to apoptotic pathway of death. [ABSTRACT FROM AUTHOR]

Nanomedicine has garnered significant attention due to the advantages it offers in the treatment of cancer-related disorders, some of the deadliest diseases affecting human lives. Conventional medication formulations often encounter issues of instability or insolubility in biological environments, resulting in low bioavailability. Nanocarriers play a crucial role in transporting and safeguarding drugs at specific sites of action, enabling gradual release under particular conditions. This study focuses on methotrexate (MTx) and cytarabine (Cyt), essential antitumoral drugs, loaded into PEGylated squalene micellar structures to enhance therapeutic effectiveness and minimize drawbacks. The micelles were prepared using ultrasound-assisted methods in both water and phosphate buffer saline solutions. Evaluation of drug-loaded micelles encompassed parameters such as particle size, colloidal stability, surface charge, morphology, encapsulation efficiency, drug loading capacity, and in vitro release profiles under simulated physiological and tumoral conditions. In vitro cell inhibition studies conducted on MCF-7 and HeLa cell lines demonstrated higher antitumoral activity for the drug-encapsulated micelles compared to free drugs. The encapsulation effectively addressed the burst effect, providing sustained release for at least 48 h while enhancing the drug's protection under physiological conditions. [ABSTRACT FROM AUTHOR]

Endophytes are micro-organism recognised that living beneficial inside the host plant produced secondary metabolites with biological activity such as anticancer, antitumor, antifungal and antibacterial. In this study, we investigated the endophytic fungus Lasiodiplodia theobromae from the root of Aglaia argentea Blume. A. argentea have been phytochemically investigated previously with unique biological activity such as cytotoxic rocaglate derivatives and dammarane-type triterpenoids. In a continuing project on the bioactive compounds from A. argantea, we have explored endophytic fungi isolated from this plant. Three steroids, ergosterol (1), ergosterol peroxide (2) and stigmasterol (3) have been isolated from endophytic fungus, Lasiodiplodia theobromae derived from the root of Aglaia argentea Blume. The steroids were isolated by vacuum chromatography and column chromatography, the chemical structure was established following the analysis of 1D-NMR, 2D-NMR, IR, MS and by comparison with previously reported spectra data. Ergosterol peroxide (2) and stigmasterol (3) were reported for the first time isolated from Lasiodiplodia theobromae endophytic fungus. Cytotoxic activities of the compounds were tested with resazurin assay against HeLa cervical cancer cells, compound 2 displayed strongest cytotoxic activities against HeLa cervical cancer cells with IC50 values of 0.28 µM, while compounds 1 and 3 showed IC50 values of 0.34 µM and 27.32 µM, respectively. [ABSTRACT FROM AUTHOR]

Sesquiterpenoids are terpenoid derivative compounds that have a diverse chemical structure and pharmacological effects. Sesquiterpenoids can be found in many plants of Aglaia which is the large source of natural compounds in the Meliaceae family. This investigation was intended to elucidate the structure of sesquiterpenoids from Aglaia cucullata peel fruit and their cytotoxicity against two human cancer cell lines. n-hexane extracts were separated by various chromatographic methods to yield three sesquiterpenoids. These sesquiterpenoids were identified by spectroscopy analysis (HR-TOFMS, IR, ¹H, 13C-NMR, DEPT-135) as well as compared with spectral data which reported previously. The sesquiterpenoid compounds 1-3 were identified as spathulenol (1), alismol (2), and 10-oxoisodauc-3-en-15-al (3). The cytotoxic activity of three sesquiterpenoid compounds were tested against B16-F10 skin cancer cell and HeLa cervical cancer cell using the PrestoBlue method. Compound 2 exhibited the highest activity against both HeLa and B16-F10 cancer cell lines with IC50 218.33 µM and 258.90 µM, respectively. [ABSTRACT FROM AUTHOR]

Fluorescence microscopy is a fundamental tool in the life sciences, but the availability of sophisticated equipment required to yield high-quality, quantitative data is a major bottleneck in data production in many laboratories worldwide. This problem has long been recognized and the abundancy of low-cost electronics and the simplification of fabrication through 3D-printing have led to the emergence of open-source scientific hardware as a research field. Cost effective fluorescence microscopes can be assembled from cheaply mass-produced components, but lag behind commercial solutions in image quality. On the other hand, blueprints of sophisticated microscopes such as light-sheet or super-resolution systems, custom-assembled from high quality parts, are available, but require a high level of expertise from the user. Here, we combine the UC2 microscopy toolbox with high-quality components and integrated electronics and software to assemble an automated high-resolution fluorescence microscope. Using this microscope, we demonstrate high resolution fluorescence imaging for fixed and live samples. When operated inside an incubator, long-term live-cell imaging over several days was possible. Our microscope reaches single molecule sensitivity, and we performed single particle tracking and SMLM super-resolution microscopy experiments in cells. Our setup costs a fraction of its commercially available counterparts but still provides a maximum of capabilities and image quality. We thus provide a proof of concept that high quality scientific data can be generated by lay users with a low-budget system and open-source software. Our system can be used for routine imaging in laboratories that do not have the means to acquire commercial systems and through its affordability can serve as teaching material to students.

Breast and cervical cancers are the leading cause of death in women, and chemotherapy with cytotoxins is the usual treatment. This study evaluated the cytotoxicity of guava leaf (Psidium guajava L.) extracts as an alternative chemotherapeutic drug. Although many studies related to the cytotoxic effects of guava leaf (Psidium guajava L.) on cancer cells have been reported, the effects of guava leaf fractions on human breast and cervical cancer cells (T47D, MCF-7, and HeLa) have never been evaluated. Herein, we researched candidate activities of ethanol, ethyl acetate, and n-extracts from guava leaf fractions and their effect on various human cancer cell lines (T47D, MCF-7, and HeLa cells). The cytotoxicity test was carried out using the microtetrazolium assay for all fractions. We confirmed and showed the in vitro antitumor activity of guava leaf (Psidium guajava L.) fractions in human breast and cervical cancer cells. We found that the effectiveness of anticancer activity increased from ethanol to ethyl acetate to n-hexane fraction. This work underlines the potential of n-hexane fraction as a chemotherapeutic drug. These novel results have important implications for further isolation, identification, and characterization of Psidium guajava L.-based anti-cancer extracts.