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Introduction: Modern cancer treatment strategies aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eradicate the cancer cells. To overcome a relatively short-lived response due to resistance to the administered drugs, combination therapies have been pursued. Objective: The objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the broader implications, and to expand the outlook, of such therapeutic approaches. Specifically, we investigated the systems-level response of a breast cancer cell line model to a mixture of kinase inhibitors that has not been adopted yet as a standard therapeutic regime. Methods: Two critical pathways that sustain the growth and survival of cancer cells, EGFR and PI3K/AKT, were inhibited in SKBR3/HER2+ breast cancer cells with Lapatinib (Tyr kinase inhibitor) and Ipatasertib (Ser/Thr kinase inhibitor), and the landscape of the affected biological processes was investigated with proteomic technologies. Results: Over 800 proteins matched by three unique peptide sequences were affected by exposing the cells to the drugs. The work corroborated the antiproliferative activity of Lapatinib and Ipatasertib and uncovered a range of impacted cancer-supportive hallmark processes, among which immune response, adhesion, and migration emerged as particularly relevant to the ability of drugs to effectively suppress the proliferation and dissemination of cancer cells. Changes in the expression of key cancer drivers such as oncogenes, tumor suppressors, EMT and angiogenesis regulators underscored the inhibitory effectiveness of drugs on cancer proliferation. The supplementation of Lapatinib with Ipatasertib further affected additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the impacted proteins represent approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners. Conclusion: Altogether, the exposure of SKBR3/HER2+ cells to Lapatinib and Ipatasertib kinase inhibitors uncovered a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ ERBB2 and PI3K/AKT pathways. [ABSTRACT FROM AUTHOR]

IntroductionModern cancer treatment strategies aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eradicate the cancer cells. To overcome a relatively short-lived response due to resistance to the administered drugs, combination therapies have been pursued.ObjectiveThe objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the broader implications, and to expand the outlook, of such therapeutic approaches. Specifically, we investigated the systems-level response of a breast cancer cell line model to a mixture of kinase inhibitors that has not been adopted yet as a standard therapeutic regime.MethodsTwo critical pathways that sustain the growth and survival of cancer cells, EGFR and PI3K/AKT, were inhibited in SKBR3/HER2+ breast cancer cells with Lapatinib (Tyr kinase inhibitor) and Ipatasertib (Ser/Thr kinase inhibitor), and the landscape of the affected biological processes was investigated with proteomic technologies.ResultsOver 800 proteins matched by three unique peptide sequences were affected by exposing the cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib and uncovered a range of impacted cancer-supportive hallmark processes, among which immune response, adhesion, and migration emerged as particularly relevant to the ability of drugs to effectively suppress the proliferation and dissemination of cancer cells. Changes in the expression of key cancer drivers such as oncogenes, tumor suppressors, EMT and angiogenesis regulators underscored the inhibitory effectiveness of drugs on cancer proliferation. The supplementation of Lapatinib with Ipatasertib further affected additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the impacted proteins represent approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners.ConclusionAltogether, the exposure of SKBR3/HER2+ cells to Lapatinib and Ipatasertib kinase inhibitors uncovered a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways.

Targeted delivery of a toxin substance to cancer cells is one of the most recent cancer treatment options. Mistletoe Lectin-1 (ML1) in Viscum album L. is a Ribosome-inactivating proteins with anticancer properties. Therefore, it appears that a recombinant protein with selective permeability can be generated by fusing ML1 protein with Shiga toxin B, which can bind to Gb3 receptor that is abundantly expressed on cancer cells. In this study, we sought to produce and purify a fusion protein containing ML1 fused to STxB and evaluate its cytotoxic activities. The ML1-STxB fusion protein coding sequence was cloned into the pET28a plasmid, then was transformed into E. coli BL21-DE3 cells. Following induction of protein expression, Ni-NTA affinity chromatography was used to purify the protein. Using SDS-PAGE and western blotting, the expression and purification processes were validated. On the SkBr3 cell line, the cytotoxic effects of the recombinant proteins were evaluated. On SDS-PAGE and western blotting membrane, analysis of purified proteins revealed a band of approximately 41 kDa for rML1-STxB. Ultimately, statistical analysis demonstrated that rML1-STxB exerted significant cytotoxic effects on SkBr3 cells at 18.09 and 22.52 ng/L. The production, purification, and encapsulation of rML1-STxB fusion protein with potential cancer cell-specific toxicity were successful. However, additional research must be conducted on the cytotoxic effects of this fusion protein on other malignant cell lines and in vivo cancer models. [ABSTRACT FROM AUTHOR]

Despite the use of the highly specific anti-HER2 receptor (trastuzumab) therapy, HER2-positive breast cancers account for 20–30% of all breast cancer carcinomas, with HER2 status a challenge to treatment interventions. The heparan sulfate proteoglycans (HSPGs) are prominently expressed in the extracellular matrix (ECM), mediate breast cancer proliferation, development, and metastasis with most studies to date conducted in animal models. This study examined HSPGs in HER2-positive human breast cancer cell lines and their contribution to cancer cell proliferation. The study examined the cells following enhancement (via the addition of heparin) and knockdown (KD; using short interfering RNA, siRNA) of HSPG core proteins. The interaction of HSPG core proteins and AKT signalling molecules was examined to identify any influence of this signalling pathway on cancer cell proliferation. Our findings illustrated the HSPG syndecan-4 (SDC4) core protein significantly regulates cell proliferation with increased BC cell proliferation following heparin addition to cultures and decreased cell number following SDC4 KD. In addition, along with SDC4, significant changes in CK19/AKT signalling were identified as mediators of BC HER2-positive BC cell proliferation. This study provides evidence for a cell growth regulatory axis involving HSPGs/CK19 and AKT that represents a potential molecular target to prevent proliferation of HER2-positive breast cancer cells. Hypothetical schematic model demonstrating the role of CK19 in mediating syndecan SDC4 and subsequent regulation of AKT signalling. SDC4 is hypothesised to negatively regulate CK19, leading to enhanced AKT protein expression. Knockdown of SDC4 results in decreased cell proliferation in HER2-positive BC.▪ • CK19 gene expresses in Luminal and HER2-positive, not in Triple-negative BCs. • Heparin treatment enhances HER2-positive BC cell proliferation. • SDC4 KD inhibits the cell proliferation characteristics in HER2-positive BC. • SDC4 regulates HER2-positive BC proliferation via the CK19/AKT signalling pathway. • CK19 may be a potential molecular target for HER2-positive BC treatment. [ABSTRACT FROM AUTHOR]

The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton's tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression. [ABSTRACT FROM AUTHOR]

The repurposing strategy of converting nimesulide from an anti-fever drug to an anti-cancer agent by modifying its main structure targeting HSP27 is gaining great attention these days. The goal of this study focuses on synthesizing a new nimesulide derivative with new ligands that have biological anti-cancer activities in different cancer models using the in-vitro assay. Nimesulide derivative L1 was synthesized, characterized by 1H NMR, 13C NMR, FTIR, melting point, mass spectra, and TGA analysis. A single crystal was diffracted and showed colorless block group P-1. The results revealed that L1 demonstrates potent anti-cancer activity with lung (H292), ovarian (SKOV3), and breast (SKBR3) cancer cell lines in-vitro models with IC50 values below 8.8 µM.

To obtain this dataset, two human HER2-positive breast cancer cell lines (SKBR3 and MDA-MB-453 cell lines) were cultured in basal growth media to 80% confluence. Cells were passaged and total RNA extracted, RNA converted to cDNA and diluted to a working concentration of 40 ng/µL. Gene expression panels of cancer markers including Fibroblast growth factors (FGF), FGF receptors (FGFRs), cyclin-dependent kinases, cytokeratins, and WNT pathway components were then examined using Q-PCR. Gene expression was normalised against the expression of the endogenous gene 18S. This article describes the data used in the research article “Syndecan-4 regulates the HER2-positive breast cancer cell proliferation cells via CK19/AKT signaling” [1]. The data presented demonstrates the range of gene expression profiles of these cells and aims to provide more detail of all gene expression changes observed in these cell lines.

Doxycycline capped gold nanoparticles (doxy-Au(0) NPs) were prepared in an aqueous medium. Particle size and shape were determined by Transmission electron microscopy which showed the monodispersed morphology. The Fourier transform infrared spectra were represented the interaction of doxycycline with surface of doxy-Au(0) NPs. X-ray powder diffraction study gave crystalline nature of the doxy-Au(0) NPs. These doxy-Au(0) NPs have an impact on the expression levels of TRP channel genes in the breast cancer line (SKBR3) and the breast epithelial cell line (CRL-4010). Additionally, the antimicrobial activities have been evaluated to be used for multiple applications. Our results showed that the expression levels of TRP genes can be changed following the treatment of AuNPs (50 and 100 µg/mL). Furthermore, the antimicrobial activies have achieved some significant results. Finally, it has been concluded that doxy-Au(0) NPs are novel and can be used as alternative nanomedicine and extendable for control of other reducible contaminants as well. [ABSTRACT FROM AUTHOR]

Elevated levels of HER2 receptor in breast cancer can be targeted through receptor-specific peptides for precise detection and therapy by nuclear medicine approach. Previously reported retro analogue of A9 peptide had shown HER2-specificity with promising pharmacokinetic features. Hence, with an aim of further improving the circulation time of rL-A9 radiopeptide, long polyethylene glycol chain (PEG 12 ) was introduced at the N-terminus of the peptide during solid phase synthesis and influence of PEGylation on biological profile was studied. [ 177 Lu]Lu-DOTA-PEG 12 -rL-A9 demonstrated high specific cellular uptake (5.94 ± 0.09 %) in HER2-expressing human breast carcinoma SKBR3 cells and low nanomolar binding affinity (K d  = 34.58 ± 12.78 nM). Uptake in SKBR3 tumors induced in female SCID mice was higher at all the time points investigated (3, 24, 48 h) in comparison to the non-PEGylated radiopeptide, [ 177 Lu]Lu-DOTA-rL-A9. Blocking studies led to 51 % reduction in accumulation of radioactivity in the tumor indicating specificity of the radiopeptide. Improved tumor-to-stomach and tumor-to-intestine ratios for [ 177 Lu]Lu-DOTA-PEG 12 -rL-A9 compared to [ 177 Lu]Lu-DOTA-rL-A9 at 48 h shall pave the way for better contrast and delineation of metastatic sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Breast cancer is one of the most diffuse cancers in the world and despite the availability of the different drugs employed against it, the need for new and particularly more specific molecules is ever growing. In this framework, natural products are increasingly assuming an important role as new anticancer drugs. Aloe-emodin (AE) is one of the best characterized molecules in this field. The functionalization of bioactive natural products with selected peptide sequences to enhance their bioavailability and specificity of action is a powerful and promising strategy. In this study, we analyzed the cell specificity, cell viability effects, intracellular distribution, and immune cell response of a new peptide conjugate of Aloe-emodin in SKBR3 and A549 cell lines by means of viability tests, flow cytometry, and confocal microscopy. The conjugate proved to be more effective at reducing cell viability than AE in both cell lines. Furthermore, the results showed that it was mainly internalized within the SKBR3 cells, showing a nuclear localization, while A459 cells displayed mainly a cytoplasmic distribution. A preserving effect of the conjugate on NKs' cell function was also observed. The designed conjugate showed a promising specific activity towards HER2-expressing cells coupled with an enhanced water solubility and a higher cytotoxicity; thus, the resulting proof-of-concept molecule can be further improved as an anticancer compound. [ABSTRACT FROM AUTHOR]

The repurposing strategy of converting nimesulide from an anti-fever drug to an anti-cancer agent by modifying its main structure targeting HSP27 is gaining great attention these days. The goal of this study focuses on synthesizing a new nimesulide derivative with new ligands that have biological anti-cancer activities in different cancer models using the in-vitro assay. Nimesulide derivative L1 was synthesized, characterized by 1H NMR, 13C NMR, FTIR, melting point, mass spectra, and TGA analysis. A single crystal was diffracted and showed colorless block group P-1. The results revealed that L1 demonstrates potent anti-cancer activity with lung (H292), ovarian (SKOV3), and breast (SKBR3) cancer cell lines in-vitro models with IC 50 values below 8.8 µM. [ABSTRACT FROM AUTHOR]

Background/Aim: Trastuzumab and tamoxifen are two of the most widely prescribed anti-cancer drugs for breast cancer (BC). To date, few studies have explored the impact of anticancer drugs on metabolic pathways in BC. Metabolomics is an emerging technology that can identify new biomarkers for tracking therapy response and novel therapeutic targets. Materials and Methods: We employed ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to investigate changes in MCF-7 and SkBr3 cell lines treated with either tamoxifen, trastuzumab or a combination of both. The Bruker Human Metabolome Database (HMDB) metabolite library was used to match spectra and the MetaboScape software to assign each feature with a putative metabolite name or molecular formula for metabolite annotation. Results: A total of 98 metabolites were found to significantly differ in abundance in MCF-7 and SkBr3 treated cells. Moreover, the metabolic profile of the combination medication is similar to that of tamoxifen alone, according to functional enrichment analysis. Conclusion: Tamoxifen/trastuzumab treatment had a significant effect on pathways essential for the control of energy-production, which have previously been linked to cancer progression, and aggressiveness. [ABSTRACT FROM AUTHOR]

Introduction: Modern cancer treatment strategies aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eradicate the cancer cells. To overcome a relatively short-lived response due to resistance to the administered drugs, combination therapies have been pursued., Objective: The objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the broader implications, and to expand the outlook, of such therapeutic approaches. Specifically, we investigated the systems-level response of a breast cancer cell line model to a mixture of kinase inhibitors that has not been adopted yet as a standard therapeutic regime., Methods: Two critical pathways that sustain the growth and survival of cancer cells, EGFR and PI3K/AKT, were inhibited in SKBR3/HER2+ breast cancer cells with Lapatinib (Tyr kinase inhibitor) and Ipatasertib (Ser/Thr kinase inhibitor), and the landscape of the affected biological processes was investigated with proteomic technologies., Results: Over 800 proteins matched by three unique peptide sequences were affected by exposing the cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib and uncovered a range of impacted cancer-supportive hallmark processes, among which immune response, adhesion, and migration emerged as particularly relevant to the ability of drugs to effectively suppress the proliferation and dissemination of cancer cells. Changes in the expression of key cancer drivers such as oncogenes, tumor suppressors, EMT and angiogenesis regulators underscored the inhibitory effectiveness of drugs on cancer proliferation. The supplementation of Lapatinib with Ipatasertib further affected additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the impacted proteins represent approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners., Conclusion: Altogether, the exposure of SKBR3/HER2+ cells to Lapatinib and Ipatasertib kinase inhibitors uncovered a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karcini, Mercier and Lazar.)

Breast cancer is one of the most diffuse cancers in the world and despite the availability of the different drugs employed against it, the need for new and particularly more specific molecules is ever growing. In this framework, natural products are increasingly assuming an important role as new anticancer drugs. Aloe-emodin (AE) is one of the best characterized molecules in this field. The functionalization of bioactive natural products with selected peptide sequences to enhance their bioavailability and specificity of action is a powerful and promising strategy. In this study, we analyzed the cell specificity, cell viability effects, intracellular distribution, and immune cell response of a new peptide conjugate of Aloe-emodin in SKBR3 and A549 cell lines by means of viability tests, flow cytometry, and confocal microscopy. The conjugate proved to be more effective at reducing cell viability than AE in both cell lines. Furthermore, the results showed that it was mainly internalized within the SKBR3 cells, showing a nuclear localization, while A459 cells displayed mainly a cytoplasmic distribution. A preserving effect of the conjugate on NKs’ cell function was also observed. The designed conjugate showed a promising specific activity towards HER2-expressing cells coupled with an enhanced water solubility and a higher cytotoxicity; thus, the resulting proof-of-concept molecule can be further improved as an anticancer compound.

Purpose: Dysregulation of HER2 signaling pathway in breast cancer is well documented. Our bioinformatics analysis predicted hsa-miR-512-3p (miR-512-3p) as a bona fide regulator of HER2 as well as HER3, PIK3R2, and AKT1 genes. Then, we intended to examine the effect of miR-512-3p on the predicted target genes that are involved in HER2 signaling pathway. Methods and results: RT-qPCR results indicated lower expression of miR-512-3p in breast cancer specimens, compared to their normal pairs. Overexpression of miR-512-3p resulted in HER2, HER3, PIK3R2, and AKT1 gene downregulation, detected by RT-qPCR and the result was confirmed by western analysis and ELIZA test against p-AKT, BAX, FADD, and HER2 proteins in SKBR3 cells, respectively. Then, dual-luciferase assay supported the direct interaction of miR-512-3p with 3′UTR sequences of HER2, HER3, PIK3R2, and AKT1 target genes. When miR-512-3p was overexpressed, BAX/BCL2 expression ratio and proportion of sub-G1 cell population were increased in transfected SKBR3 cells, detected by RT-qPCR and flow cytometry, respectively. These results were consistent with the decreased viability of transfected cells, documented by MTT assay. In addition, results were consistent with the upregulation of BAX, BAK, BOK, PTEN, P53, and P21 genes and downregulation of CCND1 gene in SKBR3 cells. Although the overexpression of miR-512 resulted in cell cycle arrest at Sub-G1 stage in MDA-MB-231 cells, this effect seemed independent of targeting HER2, HER3, PIK3R2, and AKT1 target genes. Conclusion: Overall, results indicated that miR-512-3p acts as a cell-type-specific tumor suppressor, through targeting HER2, HER3, PIK3R2, and AKT1 transcripts. These results suggest miR-512-3p as a potential candidate marker for breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Breast cancer is one of the most common types of cancers and is the second leading cause of death form of cancer in women. In recent years, many scientific and medical studies have shown that Green tea has anti-proliferative, anti-mutagenic, anti-oxidant, antibacterial and antiviral effects. Some Green tea polyphenols have anti-cancer activity. In the present study, the effect of Green tea extract was evaluated on the Breast cancer cell line (SK-BR-3) and compared with human fibroblast cell line (HU-02). Materials and Methods: SK-BR-3 and HU-02 cell lines were treated for 24, 48 and 72 hours with different concentrations of Green tea (50, 100, 200, 400 and 800 μg/ml). Then, Bioavailability was analyzed by MTT kit and Apoptosis was analyzed by flow cytometry using an Annexin V-FITS Kit. Results: With increasing concentrations of Green tea extract in dose and time dependent manner, bioavailability of cells showed a decrease as compared to control group. Increased incidence of apoptosis was significantly higher in other experimental groups than the control group, while the concentration of 800 μg/ml of Green tea extract was more effective in SKBR3 cell line. Green tea did not show significant effect in HU-02 cells. Conclusion: Due to the fact that cell proliferation and abnormal apoptosis are one of the main characteristics of cancer cells, Green tea can be used to reduce cell proliferation and increase apoptosis in prevention and treatment of Breast cancer.

Introduction: The Vismia genus belongs to the Hypericaceae family and comprises around 57 species of which 17 have been located in Venezuela. Previous investigations have been carried out in extracts as well as pure isolated compounds, revealing antimicrobial, antioxidant and anti-HIV, among other, biological activities. Objective: This investigation aims to determine the cytotoxic activity of essential oils from leaves of Vismia baccifera Triana & Planch (VBJ and VBV) and Vismia macrophylla Kunth (VM) collected in three different locations of the Venezuelan Andean region. Methods: Essential oils obtained by hydrodistillation were analyzed using gas chromatography-mass spectrometry (GC-MS) and their cytotoxic activity was analyzed following the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Human tumor cell lines from SKBr3, MCF-7 and PANC-1, two breast carcinomas and one pancreatic adenocarcinoma of ductal type, were tested with the oil samples and human dermis fibroblasts were used as non-tumor cells. Results: β-caryophyllene and trans-caryophyllene were present as major components in VBJ and VBV, respectively, while γ-bisabolene was the main component in the VM sample. Anticancer activity was observed on V. baccifera essential oil against SKBr3, MCF-7 and PANC-1. The selectivity index showed that VBV is highly selective against the SKBr3 cell line and has no activity against non-tumor cells. Conclusions: These results are considered a contribution to natural products research and may provide supportive data for future studies on cancer. [ABSTRACT FROM AUTHOR]

Herbal drug development is considered as an imperative part of complementary and alternative medicine. Bioactive compounds of botanical sources represent potential anti-cancer agents for modern therapeutics. Primary in vitro data of herb extracts' effects against cancer cell lines could be considered as indicators of potential toxicity to reduce the number of in vivo experiments. This study aims to review the findings of published articles concerning the in vitro efficacy of herbal extracts against breast cancer cell lines (MCF7 and SKBR3). In vitro studies of herbal extracts published until July 2018 were included in this review. Totally, nine extracts with IC50<4 exhibited the most inhibitory effect on breast cancer cell lines. This investigation has highlighted the fact that plant extracts have the potential to act as promising anticancer agents, making them appropriate components to be applied for chemoprevention or cancer treatment in case the researchers would find the right plant, the right solvent and the right fraction for the right disease. [ABSTRACT FROM AUTHOR]

Context: Cancer is a complex disease involving numerous changes in cell physiology and abnormal cell growth, which lead to malignant tumors. Many investigations are still carrying on in different areas including, natural products, to find a possible break point to this pathology. Aims: To evaluate the cytotoxic activity on different polar extracts from Vismia baccifera and Vismia macrophylla collected in two locations of the Venezuelan Andes. Methods: Cytotoxic activity assay was carried out following the colorimetric (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) MTT assay. Human tumor cell Lines from breast carcinoma without gene over-expression (MCF-7), breast carcinoma with overexpressed gene (SKBr3), prostate carcinoma (PC3) and cervix epithelial carcinoma (HeLa) were tested with different polarity solvent extracts (hexane, dichloromethane, ethyl acetate, butanol, water) from the two species under investigation. Human dermis fibroblasts were used as control cells. Mean inhibitory concentration (IC50) was calculated. Results: Extracts from V. macrophylla showed significant inhibition of cervix epithelial carcinoma with values ranging from 6.09 µg/mL to 17.51 µg/mL; breast carcinoma with an overexpressed gene with values from 12.14 µg/mL to 16.90 µg/mL and prostate carcinoma from 10.91 µg/mL to 17.70 µg/mL. V. baccifera extracts showed the strongest activity against prostate carcinoma with an IC50 value of 2.92 µg/mL. Conclusions: The present study showed evidence for the anticancer activity of Vismia baccifera and Vismia macrophylla extracts since caused growth inhibition in different cell lines at low concentrations, thus, it is considered not only an important contribution to the natural products research but bring supportive data for further investigations on cancer research.

Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay.Materials and Methods: SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope.Results: Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (PConclusion: MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates.

Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer.

Cancer is one of the most impacting life-threatening disease for the human populace. Hence, over the years we have seen a consistent interest to study and investigate new treatments to cure and prevent this disease. Medicinal plants have played a progressive part in treatment since many years. In this research study, we have explored the cytotoxicity effect of purified bioactive compound isolated from Stevia rebaudiana leaves and the key mechanism responsible for apoptosis in human breast cancer cells. The anticancer properties of Stevia rebaudiana leaves has been suggested in earlier literature. Hence, the aim of this study was to investigate the cytotoxicity of purified stevioside in human breast cancer cell lines MDA-MB-231 and SKBR3. Results showed that purified stevioside inhibited the growth of cancerous cell lines. The IC50 obtained after treatment with stevioside on cancer cells MDA-MB-231 and SKBR3 are 55 µM and 66 µM respectively. This shows purified stevioside is capable of inducing apoptosis indicating its promising anticancer activity. However, so far chemosensitization effects of stevioside on breast cancer have not been fully explained by other studies. Hence, additionally, this study also evaluates the chemosensitization potential of stevioside in combination with 5-FU. This research study shows the importance of Stevia rebaudiana as a good source of bioactive compounds with high anti-cancer property. [ABSTRACT FROM AUTHOR]

Abstract A series of 3-methyl-1-alkyl-2-(thiazol-4-yl)benzimidazol-3-ium ionic liquids were prepared synthetically in three steps with high overall isolated yields and their physicochemical and chemical structure were determined using different analysis techniques. The biological application of the synthesized ionic liquids has been evaluated in vitro against a panel of four human cancer cell lines: HT29, MDA-MB 231, K652 and SKBR3 using a MTT colorimetric assay. It can be concluded that among all of them compound 4fy containing C 18 alkyl chain and BF 4 − as counter-ion was found to significantly inhibit the growth of studied cell lines in dose-dependent manner with IC 50 values from 0.94 to 3.59 μM after 72 h of treatment. According to structure-activity relationships study, the chain length of alkyl substitution on the cation with different anions could play important role towards cytotoxicity of these ionic liquids. Therefore, these results show very promising future for the application of the ionic liquids based on thiabendazole as possible anticancer agents in cancer treatment. Graphical abstract Unlabelled Image Highlights • Novel ionic liquids based on alkyl-substituted thiabendazole were synthesized. • Anti-cancer activity of IL was investigated against four human cancer cells lines. • Effect of alkyl chain length towards in vitro antiproliferative is reported. [ABSTRACT FROM AUTHOR]

Traditional antimalarial drugs based on 4‐aminoquinolines have exhibited good antiproliferative activities against human tumor cells; however, their low relative efficacy has limited their corresponding clinical uses. In order to identify new potent anticancer agents based on 4‐aminoquinoline, we evaluated the antiproliferative activity of a series of dehydroxy isoquines and isotebuquines against five human cancer lines. HeLa and SKBr3 were significantly more sensitive to the action of tested quinolines than the A549, MCF‐7, and PC‐3 cancer lines. Compound 2h was by far the most potent derivative against four of the tested lines (except to PC3 line), exhibiting low micromolar or nanomolar IC50 values superior to adriamycin reference, low toxicities on dermis human fibroblasts (LD50 > 250 μM), and excellent selectivity indexes against the mentioned cancer cells. A structure–activity relationship analysis put in evidence that a pyrrolidine or morpholine moiety as N‐alkyl terminal substitution and the incorporation of the extra phenyl attached to aniline ring are pharmacophore essentials for improvement the anticancer activity of the studied dehydroxy isoquines and isotebuquines. From the results, compound 2h emerged as a promising anticancer candidate for further in vitro assays against resistant‐strain and in vivo studies as well as pharmacokinetic and genotoxicity studies. Mechanistic assays suggested that the most active quinoline 2h act as calcium‐activated potassium channel activator. A small series of dehydroxy isoquine and isotebuquines were identified as potential anticancer agents against a panel of five cancer cell, exhibiting from submicromolar to nanomolar ranges of IC50, as well as low relative toxicities on human fibroblast cells; pharmacologic profile superior to adriamycin reference drug in most of studied cases. Mechanistic studies suggested that the most active quinolines act as voltage‐gated K+ channel activator. [ABSTRACT FROM AUTHOR]

Astaxanthin (AST) is related to apoptosis but the details of the mechanism of how AST makes apoptosis is not clear. The present study investigated apoptotic effects of AST to SKBR3, a breast cancer cell line in detail. Cell viability assay showed cellular proliferation and morphological changes of the cells were observed under AST treatment. FACS analysis indicated that AST blocked cell cycle progression at G0/G1, suppressed proliferation dose-dependently, and induced apoptosis of the cells. The apoptosis of the cells by AST was further demonstrated through the decreased expression level of mutp53 and cleaved a PARP-1 fragment, respectively. In addition, AST induced the intrinsic apoptosis of the cells by activation of Bax/Bcl2, cleaved caspase-3, and cleaved caspase-9 as well as the phosphorylation of ERK1/2, JNK, and p38. Furthermore, AST decreased production of intracellular reactive oxygen species as well as modulated expressions of superoxide dismutases and Pontin, an anti-apoptotic factor. Co-immunoprecipitation assay revealed AST reduced interaction between Pontin and mutant p53. Taken together, these studies proved that AST regulates the expression of apoptotic molecules to induce intrinsic apoptosis of the cells, suggesting AST therapy might provide an alternative for improving the efficacies of other anti-cancer therapies for breast cancer.

Background and Aim: Breast cancer is one of the most common types of cancers and is the second leading cause of death form of cancer in women. In recent years, many scientific and medical studies have shown that Green tea has anti-proliferative, anti-mutagenic, anti-oxidant, antibacterial and antiviral effects. Some Green tea polyphenols have anti-cancer activity. In the present study, the effect of Green tea extract was evaluated on the Breast cancer cell line (SK-BR-3) and compared with human fibroblast cell line (HU-02). Materials and Methods: SK-BR-3 and HU-02 cell lines were treated for 24, 48 and 72 hours with different concentrations of Green tea (50, 100, 200, 400 and 800 μg/ml). Then, Bioavailability was analyzed by MTT kit and Apoptosis was analyzed by flow cytometry using an Annexin V-FITS Kit. Results: With increasing concentrations of Green tea extract in dose and time dependent manner, bioavailability of cells showed a decrease as compared to control group. Increased incidence of apoptosis was significantly higher in other experimental groups than the control group, while the concentration of 800 μg/ml of Green tea extract was more effective in SKBR3 cell line. Green tea did not show significant effect in HU-02 cells. Conclusion: Due to the fact that cell proliferation and abnormal apoptosis are one of the main characteristics of cancer cells, Green tea can be used to reduce cell proliferation and increase apoptosis in prevention and treatment of Breast cancer. [ABSTRACT FROM AUTHOR]

The inhibition of the G protein-coupled estrogen receptor (GPER) offers promising perspectives for the treatment of breast tumors. A peptide corresponding to part of the hinge region/AF2 domain of the human estrogen receptor α (ERα17p, residues 295–311) exerts anti-proliferative effects in various breast cancer cells including those used as triple negative breast cancer (TNBC) models. As preliminary investigations have evoked a role for the GPER in the mechanism of action of this peptide, we focused our studies on this protein using SkBr3 breast cancer cells, which are ideal for GPER evaluation. ERα17p inhibits cell growth by targeting membrane signaling. Identified as a GPER inverse agonist, it co-localizes with GPER and induces the proteasome-dependent downregulation of GPER. It also decreases the level of pEGFR (phosphorylation of epidermal growth factor receptor), pERK1/2 (phosphorylation of extracellular signal-regulated kinase), and c-fos. ERα17p is rapidly distributed in mice after intra-peritoneal injection and is found primarily in the mammary glands. The N-terminal PLMI motif, which presents analogies with the GPER antagonist PBX1, reproduces the effect of the whole ERα17p. Thus, this motif seems to direct the action of the entire peptide, as highlighted by docking and molecular dynamics studies. Consequently, the tetrapeptide PLMI, which can be claimed as the first peptidic GPER disruptor, could open new avenues for specific GPER modulators.

Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay. Materials and Methods: SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope. Results: Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (P<0.0001) at concentrations ranging from 0.01024 to 4000 nM in SKBR3 cells, and 0.0512 to 4000 nM in HEK293 cells. Our findings showed that MMAE inhibited the growth of SKBR3 and HEK293 cells in a concentration-dependent manner, with IC50 values of 3.27 ± 0.42 and 4.24 ± 0.37 nM, respectively. Conclusion: MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates. [ABSTRACT FROM AUTHOR]