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Dendritic cells (DCs) play a key role in initiating and regulating immune responses, and in addition to their roles in vivo, DCs are used as natural adjuvants for various tumor vaccines. In vitro, monocytes can be used to induce DCs, but in tumor patients, due to insufficient bone marrow hematopoiesis, extramedullary hematopoiesis and tumor-associated myeloid cells expand, and monocytes mainly exist in the form of myeloid-derived suppressor cells (MDSCs). The purpose of this experiment was to explore the differences in the differentiation and immune function of DCs induced by MDSCs in tumor patients. In a mouse model, we used normal mouse bone marrow cell-derived DCs as control cells, and in a tumor-bearing model, we induced MDSCs in the spleen to generate DCs (MDSC-DCs). Through flow cytometry, we found that the production of MDSC-DCs was significantly higher than that of control mice, and the secretion of interferon-γ of MDSC-DCs was significantly reduced. Through OVA antigen presentation experiments, we found that the antigen presentation ability of MDSC-DCs was significantly decreased. Through adoptive treatment of tumor-bearing mice cells, we found that the antitumor immune function of MDSC-DCs was significantly reduced. After that, we explored the mechanism of the decrease of immune function activity of MDSC-DCs. We determined that the surface markers of MDSC-DCs were changed by flow cytometry. Through flow sorting and RNA sequencing, we found that some pathways and key gene expression in MDSC-DCs were changed. In conclusion, this study found that the immune function of MDSC-DCs decreased and explored the mechanism of the decreased immune function activity.

The development of effective and safe therapeutic agents using 1,2,4-triazole derivatives is gaining momentum in today’s conditions. The value of such drugs is determined by the rapid and prolonged biological action, which is not accompanied by abrupt changes in homeostasis and pronounced side effects, which are characteristic of most pharmacological drugs of synthetic origin. In the context of a limited range of domestic antimicrobial and antifungal veterinary drugs on the national pharmaceutical market, one of the directions for solving this problem is the search, study, research, and development of drugs with antimicrobial and antifungal activity. The aim of this work was to study the mutagenic effects with the prediction of carcinogenicity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine with the prospect of further creation of new dosage forms for the treatment fungal pathologies of the skin. Materials and methods. Staph was used to study the effect of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in vitro Staphylococcus aureus, strain 209, its UV-2, UV-3 mutants and primary cell cultures. Accounting for gene mutations of microorganisms in the system of metabolic activation (Ames test) was carried out according to the method of L. M. Fonshtein in accordance with the requirements of “Methodological recommendations for assessing the mutagenic properties of new medicinal products” (Kyiv, 1996), supplemented by the methodology according to the recommendations of “Preclinical research of veterinary medicinal products” (edited by I. Ya. Kotsiumbas). Results. The results of studying the activity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine on a model of culture of tumor ascetic cells showed that at concentrations of 1.4 mg/ml, 0.8 mg/ml, 0.3 mg/ml, 0.015 mg/ml it was led to the regression of tumor cells of Ehrlich’s carcinoma and C-37 sarcoma. In experiments with the Nk/L y strain, the same concentrations of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine significantly slowed down cell growth. The results of the studies indicate a pronounced cytogenetic effect of thiophosfamide and sarcolysin, which suggests their metabolic activation in the body, as evidenced by a pronounced aberration of chromosomes. When comparing the cytogenetic effect of equimolar concentrations, the absence of cytogenetic activity of 4-((5-decylthio)-4-methyl-4-H-1,2,4-triazole-3-yl)methyl)morpholine was revealed. Conclusions. The positive results of studying the specific activity of 4-((5-decylthio)-4-methyl-4-Н-1,2,4-triazole-3-yl)methyl)morpholine in experiments in vitro were obtained which indicates the expediency of its extensive study in experimental animal tumors. In addition, according to these studies, no mutagenic effect was found at the doses that were used to predict carcinogenicity. Thus, it can be concluded that there is no cytogenetic effect.

Triptolide (TP), a compound isolated from a Chinese medicinal herb, possesses potent anti-tumor, immunosuppressive, and anti-inflammatory properties, but was clinically limited due to its poor solubility, bioavailability, and toxicity. Considering the environment-friendly, low-cost mechanochemical techniques and potential dissolution enhancement ability of Na2GA, an amorphous solid dispersion (Na2GA&TP-BM) consisting of TP and Na2GA were well-prepared to address these issues. The performance of Na2GA&TP-BM was improved through ball milling, such as from crystalline state to an amorphous solid dispersion, suitable nano micelle size and surface potential, and increased solubility. This change had a significant improvement of pharmacokinetic behavior in mice and could be able to extend the blood circulation time of the antitumor drug. Moreover, in vitro and in vivo anti-tumor study showed that Na2GA&TP-BM displayed more potent cytotoxicity to tumor cells. The work illustrated an environment-friendly and safe preparation of the TP formulation, which was promising to enhance the oral bioavailability and antitumor ability of TP, might be considered for efficient anticancer therapy.

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.

Abstract Background In recent years, silver nanoparticles (AgNPs) have gradually been widely used, especially in the field of anticancer medicine. Ovarian cancer (OC) is the gynaecological malignancy with the highest mortality rate, and the current treatment is still based on surgery, chemotherapy and postoperative targeted therapy. Therefore, the development of safe and effective nanoparticles for targeted therapy of OC is very important. This study aimed to prepare a new type of triangular silver nanoparticles (tAgNPs) and evaluate the anticancer properties for OC in vitro and in vivo. Methods The tAgNPs were chemically synthesized and characterized using scanning electron microscopy (SEM), ultraviolet (UV) spectrophotometry and other techniques. By performing cell-based tests, such as cell counting kit-8 (CCK-8), plate colony formation, cell apoptosis, reactive oxygen species (ROS), and western blot (WB) assays, the inhibitory effects and related mechanisms of tAgNPs on OC cells were analysed.The anticancer effect of tAgNPs in vivo was verified by a SKOV3 tumor-bearing mouse model. Results Five types of tAgNPs with different colours were successfully synthesized, with a particle size of 25–50 nm and a good dispersion. The results of in vitro experiments showed that tAgNPs treatment reduced the viability and proliferation of SKOV3 cells, arrested the cell cycle in G0/G1 phase, inhibited the expression levels of proliferation-related factors and cyclins, and promoted cell apoptosis by producing ROS and increasing caspase-3 activity. Consistent with the results of in vitro experiments, in vivo animal experiments also showed that tAgNPs significantly inhibited the proliferation of ovarian cancer. More importantly, no obvious toxic and side effects were observed. Conclusions In this study, a novel triangular AgNPs was successfully prepared. tAgNPs are very stable, significantly inhibit the proliferation of OC cells and tumour growth in tumour-bearing mice, providing a promising nanotargeted therapy for OC.

Objective: The monosaccharide composition of Poria cocos polysaccharide (PCOS) from Poria cocos residue extracted by hot water, as well as its anti-cancer, anti-inflammatory factors and immune activities were studied, providing a theoretical foundation for the development of PCOS related products. Methods: The monosaccharide composition of water-extracted PCOS was analyzed by HPLC and FTIR, and the anti-tumor and immune activities of water-extracted PCOS were studied by CCK-8 method. Results: The polysaccharide content of PCOS was 76%, mainly composed of glucose, mannose, galactose and fucose, and the molar ratio was 1:0.107:0.079:0.018, with obvious polysaccharide characteristic absorption peak. The proliferation of gastric cancer cells, breast cancer cells, and liver cancer cells was decreased, with the best inhibition impact on gastric cancer cells (IC50=1096 µg/mL), and spleen lymphocyte proliferation in mice was enhanced. Conclusion: The water-extracted PCOS has good anti-cancer and immune activities in vitro.

Abstract The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver‐resident NK (lr‐NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL+) lr‐NK cells by about 20% and attenuated cytotoxic activity against the Hepa1‐6 cell line by about 40%. Among various cytokine, only interleukin‐33 (IL‐33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr‐NK cells highly expressed ST2/IL‐33R, IL‐33 co‐culture significantly suppressed TRAIL expression on lr‐NK cells by about 50%, and IL‐33 administration markedly decreased TRAIL expression and cytotoxic activity of lr‐NK cells. Furthermore, the TRAIL+ NK cells population was maintained by anti‐IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL‐33 decreased TRAIL expression in lr‐NK cells via AKT–forkhead box O (FoxO) and mitogen‐activated protein kinase (MAPK) signaling. Conclusion: This work demonstrates that PHT suppresses the TRAIL+ lr‐NK cell population and antitumor activities in the liver. Additionally, Akt‐FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt‐NK cells via IL‐33 receptor in mice.

Metal‐polarized aza‐ortho‐quinone methides (aza‐o‐QMs) are a unique and efficient handle for azaheterocycle synthesis. Despite great achievements, the potential of these reactive intermediates has not yet been fully exploited, especially the new reaction modes. Herein, we disclosed an unprecedented dearomatization process of metal‐polarized aza‐o‐QMs, affording transient dearomatized spiroaziridine intermediates. Based on this serendipity, we accomplished three sequential dearomatization‐rearomatization reactions of benzimidazolines with aza‐sulfur ylides, enabling the divergent synthesis of bis‐nitrogen heterocycles with high efficiency and flexibility. Moreover, experimental and theoretical studies were performed to explain the proposed mechanisms and observed selectivity. Further cellular evaluation of the dibenzodiazepine products identified a hit compound for new antitumor drugs. [ABSTRACT FROM AUTHOR]

A series of indazole derivatives were designed and synthesized by molecular hybridization strategy, and these compounds were evaluated the inhibitory activities against human cancer cell lines of lung (A549), chronic myeloid leukemia (K562), prostate (PC-3), and hepatoma (Hep-G2) by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Among these, compound 6o exhibited a promising inhibitory effect against the K562 cell line with the IC50 (50% inhibition concentration) value of 5.15 µM, and this compound showed great selectivity for normal cell (HEK-293, IC50 = 33.2 µM). Moreover, compound 6o was confirmed to affect apoptosis and cell cycle possibly by inhibiting Bcl2 family members and the p53/MDM2 pathway in a concentration-dependent manner. Overall, this study indicates that compound 6o could be a promising scaffold to develop an effective and low-toxic anticancer agent. [ABSTRACT FROM AUTHOR]

Eight new N-acylhydrazones were synthesized from betulin diacetate by its low-temperature ozonolysis to obtain 3β,3,28-diacetoxyoxy-20-oxo-29-norlupan and condensation of the latter with capric, cyclohexanoic, benzoic, o-hydroxy-, p-hydroxy-, p-methoxybenzoic, isonicotinic, and nicotinic hydrazides. The synthesized compounds were tested for in vitro cytotoxic activity against a number of cancer cell lines. The derivatives of salicylic, isonicotinic, and nicotinic hydrazides showed moderate activity against HepG2 human hepatocellular carcinoma, HTC-116 human colon cancer, THP-1 leukemia, and Jurkat acute T-cell leukemia cells. [ABSTRACT FROM AUTHOR]

A new series of nanostructured materials was obtained by functionalization of SBA-15 mesoporous silica with Ru(II) and Ru(III) complexes bearing Schiff base ligands derived from salicylaldehyde and various amines (1,2-diaminocyclohexane, 1,2-phenylenediamine, ethylenediamine, 1,3-diamino-2-propanol, N,N-dimethylethylenediamine, 2-aminomethyl-pyridine, and 2-(2-aminoethyl)-pyridine). The incorporation of ruthenium complexes into the porous structure of SBA-15 and the structural, morphological, and textural features of the resulting nanostructured materials were investigated by FTIR, XPS, TG/DTA, zeta potential, SEM, and N2 physisorption. The ruthenium complex-loaded SBA-15 silica samples were tested against A549 lung tumor cells and MRC-5 normal lung fibroblasts. A dose-dependent effect was observed, with the highest antitumoral efficiency being recorded for the material containing [Ru(Salen)(PPh3)Cl] (50%/90% decrease in the A549 cells' viability at a concentration of 70 μg/mL/200 μg/mL after 24 h incubation). The other hybrid materials have also shown good cytotoxicity against cancer cells, depending on the ligand included in the ruthenium complex. The antibacterial assay revealed an inhibitory effect for all samples, the most active being those containing [Ru(Salen)(PPh3)Cl], [Ru(Saldiam)(PPh3)Cl], and [Ru(Salaepy)(PPh3)Cl], especially against Staphylococcus aureus and Enterococcus faecalis Gram-positive strains. In conclusion, these nanostructured hybrid materials could represent valuable tools for the development of multi-pharmacologically active compounds with antiproliferative, antibacterial, and antibiofilm activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is one of the major current public health threats worldwide that needs new forms of treatment. The seeds of Euterpe oleracea fruit, popularly known as açaí, are part of the fruit that are rejected during its processing for consumption, although the seeds have several compounds with pharmacological potential. This study aimed to evaluate the effect of açai seed extract against cancer cells in vitro and in vivo in animals with an Ehrlich tumor, an inflammatory mammary type of cancer. The açai seed extract displayed a rich chemical composition with a high content of catechin/epicatechin. Prostate cancer cell lines were killed by açai seed extract treatment in vitro. Animals with an Ehrlich tumor treated with açai seed extract showed a decrease in tumor size and an enhancement of the immunological response against the tumor. All these results point to a promising antitumor effect of açai seed extract that should be further clarified. Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins—polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects—almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties. [ABSTRACT FROM AUTHOR]

About twenty molecules sharing 1H-chromeno[3,2-c]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1H-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-c]pyridin-10-ones (1,2,3,4-THCP-10-ones, 1) or 2,3-dihydro-2-methyl-1H-chromeno[3,2-c]pyridines (2,3-DHPCs, 2). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives 2 inhibit MAO A (IC50 about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one 3a, bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC50 0.51 μM) and moderate inhibitor of both ChEs (IC50s 7–8 μM); (iii) the 1H-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog 6c achieving MAO B IC50 of 3.51 μM. The MAO B inhibitor 3a deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson's disease and neuroprotectant for Alzheimer's disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog 6c exerts anti-tumor activity with IC50s in the range 4.83–11.3 μM. [ABSTRACT FROM AUTHOR]

Helichrysum arenarium (L) Moench (sandy everlasting) is a valuable plant for therapy, having multiple applications in traditional medicine, applications which are confirmed nowadays by science. The main polyphenols found in sandy everlasting flowers were shown to have antioxidant and UV-screen effects. In order to expand our knowledge concerning the synergistic therapeutic effects of the polyphenols from Helichrysum arenarium (L) flowers, an extract was prepared using 50% ethanol as extraction phase, followed by the removing of ethanol using a Royeyov IKA RV10 rotary evaporator. The chemical analysis of the extract consisted in the assessment of total polyphenol content (Folin-Ciocalteu) and flavonoid fingerprint (high-performance thin-layer chromatography -HPTLC). For the polyphenolic extract there were assessed the antioxidant activity (measured by two methods: ferric reducing antioxidant power (FRAP) and radical scavenging activity with DPPH)) and sun protection factor (SPF) (assessed using an in vitro spectrometric method). Furthermore, the cytotoxic and antitumor effects were evaluated on two cell lines: pMSCs (palatal mesenchymal stem cells) and HeLa (ATTC® CCL-2™) cell line (epithelial cells derived from human cervical adenocarcinoma). The extract contains apigenin-7-glucoside, luteolin-7-glucoside and rosmarinic acid. The extract shows a significant UV-screen protection effect, particularly for UVB radiations. The extract has not cytotoxic effects on palatal mesenchymal stem cells. The cytometric apoptosis assay on HeLa cell line reveals the in vitro antitumor effect of the extract. The results highlights both antioxidant and antitumor activity as well as the UV-screen effect of the polyphenols from Helichrysum arenarium flowers. All these data not only confirm the high antioxidant properties of the polyphenols contained in the sandy everlasting flowers, but also open new ways of applications for therapy of this plant. [ABSTRACT FROM AUTHOR]

One of the objectives of this study consists of the assessment of the antitumor activity of several extracts from three selected plant species: Xanthium spinosum L., Trifolium pratense L., and Coffea arabica L. and also a comparative study of this biological activity, with the aim of establishing a superior herbal extract for antitumor benefits. The phytochemical profile of the extracts was established by HPLC-MS analysis. Further, the selected extracts were screened in vitro for their antitumor activity and antioxidant potential on two cancer cell lines: A549—human lung adenocarcinoma and T47D-KBluc—human breast carcinoma and on normal cells. One extract per plant was selected for in vivo assessment of antitumor activity in an Ehrlich ascites mouse model. The extracts presented high content of antitumor compounds such as caffeoylquinic acids in the case of X. spinosum L. (7.22 µg/mL—xanthatin, 4.611 µg/mL—4-O-caffeoylquinic acid) and green coffee beans (10.008 µg/mL—cafestol, 265.507 µg/mL—4-O-caffeoylquinic acid), as well as isoflavones in the case of T. pratense L. (6806.60 ng/mL—ononin, 102.78 µg/mL—biochanin A). Concerning the in vitro results, the X. spinosum L. extracts presented the strongest anticancerous and antioxidant effects. In vivo, ascites cell viability decreased after T. pratense L. and green coffee bean extracts administration, whereas the oxidative stress reduction potential was important in tumor samples after T. pratense L. Cell viability was also decreased after administration of cyclophosphamide associated with X. spinosum L. and T. pratense L. extracts, respectively. These results suggested that T. pratense L. or X. spinosum L. extracts in combination with chemotherapy can induce lipid peroxidation in tumor cells and decrease the tumor viability especially, T. pratense L. extract. [ABSTRACT FROM AUTHOR]

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Ziziphus jujuba Mill. is a deciduous shrub, belonging to the Rhamnaceae family. Phytochemical investigation of Z. jujuba seeds showed the presence of three undescribed 8,4′-type oxyneolignans (1-3). Their structures were elucidated by comprehensive spectroscopic analyses. All isolated compounds were tested for antitumor activity against two human hepatoma cells (Hep3B and HepG2) and exhibited moderate cytotoxicity (IC50: 33.79-49.62 µM). [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs). The results showed that most of derivatives totally inhibit PDK1 and PDK4. Molecular docking analysis was executed to predict the possible binding mode of these derivatives using ligand-based homology modeling technique. Evaluation of the capability of new triazines to inhibit the cell growth in 2D and 3D KRAS-wild-type (BxPC-3) and KRAS-mutant (PSN-1) PDAC cell line, was carried out. The results showed the capacity of the new derivatives to reduce cell growth with a major selectivity against KRAS-mutant PDAC PSN-1 on both cell models. These data demonstrated that the new triazine derivatives target PDK1 enzymatic activity and exhibit cytotoxic effects on 2D and 3D PDAC cell models, thus encouraging further structure manipulation for analogs development against PDAC. [ABSTRACT FROM AUTHOR]

Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use. [ABSTRACT FROM AUTHOR]

Background: Overwhelming Fe accumulation in tumor arouses strong oxidative stress. To benefit the cancer patients, Fe(II) delivered by carbon nanoparticles-Fe(II) complex (CNSI-Fe) should be visualized to ensure the successful intratumoral injection and the antitumor mechanisms should be investigated at molecular level. Results: Intracellular Fe accumulations associating with the uptakes of CNSI-Fe were observed both in vitro and in vivo. The retention of Fe(II) in tumor over 72 h was visualized by magnetic resonance imaging. CNSI-Fe inhibited the tumor growth and expanded the lifespan of colonic tumor-bearing mice. The antitumor activity of CNSI-Fe was attributed to the increases of OH radicals and the oxidative stress in tumor cells, which resulted in cell apoptosis and ferroptosis. The transcriptome analyses confirmed the changes of ferroptosis and inflammation signaling pathways by CNSI-Fe treatment. The low toxicity of CNSI-Fe was indicated by the serum biochemistry, hematology, and histopathology. Conclusion: CNSI-Fe induced the efficient apoptosis and ferroptosis of colonic tumor for cancer therapy. Our results would benefit the clinical applications of CNSI-Fe and stimulate great interest in the nanomedicine. [ABSTRACT FROM AUTHOR]

In this study, a series of nine new 2-(cyclopentylamino)thiazol-4(5H)-one derivatives were synthesized, and their anticancer, antioxidant, and 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitory activities were tested. Anticancer activity has been assessed using the MTS (MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay against human colon carcinoma (Caco-2), human pancreatic carcinoma (PANC-1), glioma (U-118 MG), human breast carcinoma (MDA-MB-231), and skin melanoma (SK-MEL-30) cancer cell lines. Cell viability reductions, especially in the case of Caco-2, MDA-MB-231, and SK-MEL-30 lines, were observed for most compounds. In addition, the redox status was investigated and oxidative, but nitrosative stress was not noted at a concentration of 500 µM compounds tested. At the same time, a low level of reduced glutathione was observed in all cell lines when treated with compound 3g (5-(4-bromophenyl)-2-(cyclopentylamino)thiazol-4(5H)-one) that most inhibited tumor cell proliferation. However, the most interesting results were obtained in the study of inhibitory activity towards two 11β-HSD isoforms. Many compounds at a concentration of 10 µM showed significant inhibitory activity against 11β-HSD1 (11β-hydroxysteroid dehydrogenase type 1). The compound 3h (2-(cyclopentylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one) showed the strongest 11β-HSD1 inhibitory effect (IC50 = 0.07 µM) and was more selective than carbenoxolone. Therefore, it was selected as a candidate for further research. [ABSTRACT FROM AUTHOR]

Clinopodium vulgare L. is a valuable medicinal plant used for its anti-inflammatory, antibacterial and wound-healing properties. The present study describes an efficient protocol for the micropropagation of C. vulgare and compares, for the first time, the chemical content and composition and antitumor and antioxidant activities of extracts from in vitro cultivated and wild-growing plants. The best nutrient medium was found to be Murashige and Skoog (MS) supplemented with 1 mg/L BAP and 0.1 IBA mg/L, yielding on average 6.9 shoots per nodal segment. Flower aqueous extracts from in vitro plants had higher total polyphenol content (29,927.6 ± 592.1 mg/100 g vs. 27,292.8 ± 85.3 mg/100 g) and ORAC antioxidant activity (7281.3 ± 82.9 µmol TE/g vs. 7246.3 ± 62.4 µmol TE/g) compared to the flowers of wild plants. HPLC detected qualitative and quantitative differences in phenolic constituents between the in vitro cultivated and wild-growing plants' extracts. Rosmarinic acid was the major phenolic constituent, being accumulated mainly in leaves, while neochlorogenic acid was a major compound in the flowers of cultivated plants. Catechin was found only in cultivated plants, but not in wild plants or cultivated plants' stems. Aqueous extracts of both cultivated and wild plants showed significant in vitro antitumor activity against human HeLa (cervical adenocarcinoma), HT-29 (colorectal adenocarcinoma) and MCF-7 (breast cancer) cell lines. The best cytotoxic activity against most of the cancer cell lines, combined with the least detrimental effects on a non-tumor human keratinocyte cell line (HaCaT), was shown by the leaf (250 µg/mL) and flower (500 µg/mL) extracts of cultivated plants, making cultivated plants a valuable source of bioactive compounds and a suitable candidate for anticancer therapy. [ABSTRACT FROM AUTHOR]

Ganoderic acids (GAs), mainly from the traditional Chinese medicinal Ganoderma lucidum, possess antitumor, anti-metastasis and other significant pharmacological activities. Due to the difficulty to purify the GAs monomer with low yield and similar structure, the pharmacological activities of most of GA have not been clarified, which hindered their widespread application. In this study, we expressed our previously identified two CYPs, CYP5150L8 and CYP5139G1 in Saccharomyces cerevisiae to generate two plasmid-containing yeast strain Y2P, which can produce 3,28-dihydroxy-lanosta-8,24-dien-26-oic acid (DHLDOA) at concentration of 0.6 mg/L. To improve the production of DHLDOA, we transfer CYP partner, cytochrome P450 reductase, into the CYP5150 and CYP5139G1 co-expression Y2P strain to obtain 3 plasmids co-transformation strain Y3P, and used 3 antibiotics to avoid plasmid loss during cell cultivation. The DHLDOA production of S. cerevisiae Y3P reached to 2.9 and 11.1 mg/L without or with adding hygromycin, G418, and zeocin, respectively. In addition, it was found that DHLDOA was effective against non-small cell lung cancer but had low toxicity to normal cells. This study may facilitate the wide-spread application of GA-DHLDOA and further improvement of DHLDOA production by the yeast fermentation. [ABSTRACT FROM AUTHOR]

Cancer is a major health problem with significant morbidity and mortality. In addition, plants are a source of metabolites with diverse biological properties, including antitumor potential. In this study, we investigated the in vitro murine lymphoma L5178Y-R cell growth inhibition, human peripheral blood mononuclear cells (PBMC) toxicity and proliferation, and antioxidant, hemolytic, and anti-hemolytic activities of methanol extracts from 15 plants of traditional use in Mexico. Justicia spicigera caused the highest tumor cell growth inhibition with a half maximal inhibitory concentration (IC50) of 29.10 µg/mL and a selectivity index >34.36 compared with those of PBMC, whereas Mimosa tenuiflora showed the highest lymphoproliferative activity from 200 µg/mL compared with that induced by concanavalin A. In addition, M. tenuiflora showed an antioxidant effect (IC50 = 2.86 µg/mL) higher than that of ascorbic acid. Regarding the hemolytic and anti-hemolytic activity, all extracts presented significant anti-hemolytic activity. The extract of J. spicigera is emerging as a possible source of effective antineoplastic compounds. [ABSTRACT FROM AUTHOR]

Cinnamic acid is a plant metabolite with antimicrobial, anticancer, and antioxidant properties. Its synthetic derivatives are often more effective in vitro than parent compounds due to stronger biological activities. In our study, we synthesized ten new N–(4–chloro–2–mercapto–5–methylphenylsulfonyl)cinnamamide derivatives, containing two pharmacophore groups: cinnamic acid moiety and benzenesulfonamide. The antimicrobial activity of the obtained compounds was estimated using different types of Gram-positive and Gram-negative bacteria, fungus species of Candida albicans, as well as clinical strains. The compounds were evaluated on biofilm formation and biofilm formed by Staphylococcus clinical strains (methicillin–resistance S. aureus MRSA and methicillin–resistance coagulase–negative Staphylococcus MRCNS). Furthermore, blood bacteriostatic activity test was performed using S. aureus and S. epidermidis. In cytotoxic study, we performed in vitro hemolysis assay on domestic sheep peripheral blood and MTT [3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide] assay on human cervical HeLa, ovarian SKOV-3, and breast MCF-7 cancer cell lines. We also estimated antioxidant activity of ten compounds with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′–azino–bis(3–ethylbenzthiazoline–6–sulfonic acid) (ABTS) assays. Our results showed a significant antimicrobial activity of the compounds. All of them were active on Staphylococcus and Enterococcus species (MIC was 1–4 µg/mL). The compounds 16d and 16e were the most active on staphylococci clinical strains and efficiently inhibited the biofilm formation and biofilm already formed by the clinical staphylococci. Moreover, the hemolytic properties of the tested compounds occurred in higher quantities (>32.5 µg/mL) than the concentrations that inhibited both the growth of bacteria in the blood and the formation and growth of biofilm. The results of MTT assay showed that compounds 16c, 16d, 17a, and 17d demonstrated the best activity on the cancer cells (the IC50 values were below 10 µg/mL). Compound 16f was the least active on the cancer cells (IC50 was > 60 µg/mL). Antiradical tests revealed that compounds 16f and 17d had the strongest antioxidant properties within the tested group (IC50 was 310.50 ± 0.73 and 574.41 ± 1.34 µg/mL in DPPH, respectively, and 597.53 ± 1.3 and 419.18 ± 2.72 µg/mL in ABTS assay, respectively). Our study showed that the obtained cinnamamide derivatives can be used as potential antimicrobial therapeutic agents. [ABSTRACT FROM AUTHOR]

New nickel (II), cobalt (II), and several copper (II) complexes have been synthesized from the hydrazone ligand (AHTDSH; H2L); which obtained from 5‐acetyl‐4‐hydroxy‐2H‐1,3‐thiazine‐2,6(3H)‐dione with salicylaldehyde hydrazone. The structures of H2L ligand and the prepared complexes were confirmed by spectroscopic and analytical techniques. The ligand behaves as bis (monobasic bidentate) and dibasic tetradentate chelating agent via azomethine nitrogen and phenolic oxygen atoms. Octahedral geometries have been assigned for the prepared complexes. The Coats–Redfern equations were used to estimate the kinetic parameters (Ea, A, H, S, and G) of the thermal decomposition stages. The molecular structural characteristics of the ligand and its metal complexes were estimated based on density functional theory (DFT) level implemented in the Gaussian 09 software at B3LYP/6‐311G(d,p) level and the theoretical data were connected with the results of the experimental work. The anticancer activity of AHTDSH ligand and its complexes was demonstrated toward HepG2 cell lines. The interaction between the chemical and the active site of the CDK2 kinase was examined using a docking study of the hydrazone ligand and its complexes. [ABSTRACT FROM AUTHOR]

Erysolin and its two metabolites which were found in blood, ERY-GSH and ERY-NAC, were synthesized by alkylation, amination, isothiocyanation and oxidation reactions from 1-bromo-4-chlorobutane and sodium methyl mercaptide. The reaction temperature, time, feed ratios and purification method were also optimized. The synthesis method was simple, green, safe and low-cost. Erysolin, ERY-GSH and ERY-NAC showed good antitumor activities against MCF-7, HeLa, HepG2, A549 and SW480 cells, which suggested that the antitumor mechanism of erysolin can also be clarified from its metabolites in addition to itself. [ABSTRACT FROM AUTHOR]

An in vitro bioassay-guide revealed that the methanolic extract of the aerial parts of Cometes abyssinica had considerable inhibitory activity against colon (HCT-116) and hepatocellular (HepG2) carcinoma cell lines with IC50 24.4 and 29.9 µg/mL, respectively, compared to the drug reference Cisplatin. On the other hand, all studied extracts exhibited weak antioxidant activities using the DPPH scavenging assay with IC50 values between 543-826.4 µg/mL. Phytochemical investigation of the methanol and ethyl acetate extracts of C. abyssinica led to the isolation of five flavonoid compounds: Formononetin 1, Daidzein 2, Eriodictyol 3, Taxifolin 4, and kaempferitrin 5. The chemical structure of the isolated compounds was identified based on their physicochemical and spectroscopic analyses. [ABSTRACT FROM AUTHOR]

We report a series of hybrid oxoazetidine conjugated thiazoles as epidermal growth factor receptor (EGFR) inhibitors, which were synthesized and tested using a variety of in silico and in vitro studies. The compounds were found to be active against breast and hepatic cancer cell lines, with Compounds 7a, 7b, and 7e being the most potent ones. The derivatives were also evaluated for molecular docking and complementarity studies to explicate fundamental substituent groups essential for their bioactivity. Moreover, the structural activity relationship of the analogues was performed for future compound optimization. These studies advocated that the analogues have a high affinity towards EGFR with favorable anticancer potential. The study advised that the derivatives have potency against breast and hepatic cancer and can assist as an initial scaffold for further development of anti‐EGFR compounds. [ABSTRACT FROM AUTHOR]

Background Anlotinib is a multi-target tyrosine kinase inhibitor that can effectively inhibit tumor cell proliferation after receptor kinase activation caused by KIT gene mutation. Methods We tested the inhibitory effect of anlotinib in GIST cell lines with different gene mutations and evaluated the efficacy of anlotinib for patients with metastatic GIST after imatinib failure in a multicenter, single-arm, phase II study. Results In vitro, V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib. Moreover, anlotinib was able to partly suppress the activation loop mutation D820A from exon 17 while another activation loop mutation N822K, also from exon 17, was resistant to anlotinib. From September 2018 to October 2020, 64 patients from 9 Chinese medical centers were enrolled in this study. Seven patients had partial response and 39 patients had stable disease. The median PFS was 8.0 months. There was no statistical significance comparing with PFS of sunitinib second-line therapy at the same period. The most common adverse events related to anlotinib treatment were hypertension, neutropenia, and fatigue. Conclusion Anlotinib showed moderate antitumor activity in drug-resistant GIST cell lines in vitro, and good PFS and better tolerance in second-line therapy study. [ABSTRACT FROM AUTHOR]

The JAK/STAT3 signaling pathway is aberrantly hyperactivated in many cancers, promoting cell proliferation, survival, invasiveness, and metastasis. Thus, inhibitors targeting JAK/STAT3 have enormous potential for cancer treatment. Herein, we modified aldisine derivatives by introducing the isothiouronium group, which can improve the antitumor activity of the compounds. We performed a high-throughput screen of 3157 compounds and identified compounds 11a, 11b, and 11c, which contain a pyrrole [2,3-c] azepine structure linked to an isothiouronium group through different lengths of carbon alkyl chains and significantly inhibited JAK/STAT3 activities. Further results showed that compound 11c exhibited the optimal antiproliferative activity and was a pan-JAKs inhibitor capable of inhibiting constitutive and IL-6-induced STAT3 activation. In addition, compound 11c influenced STAT3 downstream gene expression (Bcl-xl, C-Myc, and Cyclin D1) and induced the apoptosis of A549 and DU145 cells in a dose-dependent manner. The antitumor effects of 11c were further demonstrated in an in vivo subcutaneous tumor xenograft experiment with DU145 cells. Taken together, we designed and synthesized a novel small molecule JAKs inhibitor targeting the JAK/STAT3 signaling pathway, which has predicted therapeutic potential for JAK/STAT3 overactivated cancer treatment. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide with a huge societal and economic impact. Clinically effective and less expensive anticancer agents derived from natural sources can help to overcome limitations and negative side effects of chemotherapy and radiotherapy. Previously, we showed that the extracellular carbohydrate polymer of a Synechocystis ΔsigF overproducing mutant displayed a strong antitumor activity towards several human tumor cell lines, by inducing high levels of apoptosis through p53 and caspase-3 activation. Here, the ΔsigF polymer was manipulated to obtain variants that were tested in a human melanoma (Mewo) cell line. Our results demonstrated that high molecular mass fractions were important for the polymer bioactivity, and that the reduction of the peptide content generated a variant with enhanced in vitro antitumor activity. This variant, and the original ΔsigF polymer, were further tested in vivo using the chick chorioallantoic membrane (CAM) assay. Both polymers significantly decreased xenografted CAM tumor growth and affected tumor morphology, by promoting less compact tumors, validating their antitumor potential in vivo. This work contributes with strategies for the design and testing tailored cyanobacterial extracellular polymers and further strengths the relevance of evaluating this type of polymers for biotechnological/biomedical applications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising non‐invasive treatment modality for tumors. However, the lack of attack targets in tumor cells greatly affects the antitumor efficiency of PDT. Mitochondria, as one of the most pivotal subcellular organelles, generated most of the energy for tumor cells and play an important role in tumor cell proliferation. PDT targeting mitochondria provides a practicable scheme for accurate and efficient antitumor treatment. Hence, the strategies of mitochondria‐based PDT using phthalocyanines or porphyrins as photosensitizers was summarized, including covalent modification of photosensitizers, delivery of drug carriers and cellular respiration in mitochondria. This review will provide guidance in the development of precision medicine for cancer treatment. [ABSTRACT FROM AUTHOR]

Venom peptides are interesting molecular models for the development of biotechnological strategies applicable in generating therapeutic agents and/or experimental tools for basic and applied research. The present study aimed to search for peptides from Bothrops atrox snake venom with anticancer potential activity against HepG2 liver tumor cell line, determine their cytotoxic action, and analyze the structure–function relationship. The novel peptide Batroxin I (M.W. 1.38 kDa) was isolated by molecular exclusion and reversed phase chromatography methods. The Batroxin I presented a selective cytotoxicity towards tumor cells, reducing the viability of HepG2 cells by 94.6% with IC50 of 0.72 μg/mL, and showing a low toxicity against peripheral blood mononuclear cells. Analysis of the apoptotic and necrotic peptide effects revealed that it induced apoptosis by intrinsic pathway activation. The amino acid sequence of Batroxin I was determined by de novo sequencing as < EKWPRPDAPIPP (where < E = pyroglutamic acid); hence, it is an unpublished peptide that belongs to the class of bradykinin-enhancing peptides and cell penetration peptide. This is one of the first reports on the cytotoxic antitumor activity of a bradykinin-enhancing peptide. Our results indicate that this peptide could serve not only as a template for the development of new drugs, but also as an adjuvant to less effective marketed drugs to treat cancer and other diseases. [ABSTRACT FROM AUTHOR]

Thiazole is a functional group used in cancer treatment modalities in synthetic and natural antitumor medications. In this context, convenient synthesis of new 5-heteroaryl-thiazoles is described via reactions of thiazolylenaminone with sulfanilamide, sulfathiazole, hydrazine hydrate, phenylhydrazine, hydroxylamine, guanidine, aminoazoles, β-dicarbonyl compounds, and diazotized aminoazoles. The constitution of the constructed thiazoles was avowed by elemental analyses and spectral data as well as alternative syntheses wherever possible. Thiazoles were also tested for their antitumor activity toward human cancer cell lines (MCF-7, HCT-116, and HepG-2) and one normal cell line (REP1). Among the synthesized thiazoles, compounds 6, 19, and 23a showed high potent antitumor profiles toward cancer cell lines and found no evidence of human toxicity. [ABSTRACT FROM AUTHOR]

Oleanolic acid has previously been shown to possess PI3K inhibitory activity, thus, the purpose of this work was to generate a series of derivatives that improve the potency. Twenty rationally designed oleanolic acid derivatives were synthesized and tested the cytotoxicity and PI3K inhibitory activity. The results suggested that attachment of additional structural elements such as association of thiazole group to A ring and insertion of phenylurea group was important for increasing activities. The most active derivative was compound II2, which exhibited PI3K inhibitory activity (IC50 = 58.42 nmol/l) and improved interaction with activity site of PI3K according with docking studies. [ABSTRACT FROM AUTHOR]

Microalgae are aerobic photosynthetic microorganisms known to man since ancient times – algal biomass has been collected and used as food for centuries. They can be found in a wide variety of habitats around the world, due to their remarkable ability to adapt to changing and often harsh environmental conditions, including temperature anomalies, drought, salinity, photooxidation and UV radiation. To survive in the complex and competitive environment in the numerous ecological niches which they populate, microalgae synthesize a wide variety of metabolites, some of which are not found in other organisms. The expanding necessity for natural, safe, and environmentally friendly renewable products gives an impetus to cultivation of microalgae, rich producers of valuable substances: proteins containing essential amino acids, unsaturated fatty acids, sterols, vitamins, pigments, polysaccharides, etc. Many of these substances exhibit various biological activities and pharmacological properties, such as antibacterial, antifungal, antiviral and antitumor activity, immunostimulatory, anti-inflammatory, fibrinolytic, antidiabetic and antioxidant properties, and are used or have the potential for application as medicinal agents, functional foods, in cosmetics and pharmacy. Advances in the modern microalgal biotechnology contribute to increasing the number of cultivated species and expanding their fields of application, including in agriculture as biostimulants, biopesticides, feed and feed additives for animals. As a result of intensive targeted research worldwide, a number of other microalgae species/strains have been identified, apart from the industrially cultivated ones, possessing the necessary characteristics and potential for commercial production. [ABSTRACT FROM AUTHOR]

Background: Silver nanoparticles (AgNPs) are attractive substrates for new medicinal treatments. Biochar is pyrolyzed biomass. Its porous architecture allows it to hold and gather minuscule particles, through which nanoparticles can accumulate in its porous structure. This study examined AgNPs' antibacterial and anticancer properties alone and combined with biochar. Methods: The fungus Emericella dentata was responsible for biosynthesis of AgNPs. The characterization of AgNPs using STEM images and a Zetasizer was carried out. Accordingly, the antibacterial and antiproliferation activity of AgNPs and biochar was studied using MIC and MTT assays, respectively. To evaluate the antiangiogenic and anti-inflammatory effects of AgNPs with biochar, VEGF and cytokines including TNF alpha, IL-6 and IL-beta were tested using an ELISA assay. Results: The size of the AgNPs ranged from 10 to 80 nm, with more than 70% of them being smaller than 40 nm. The combination of AgNPs and biochar enhanced the antibacterial activity against all tested bacteria. Furthermore, this combination showed antiproliferative properties against HT29 cancer cells with high selectivity to fibroblasts at low concentrations. AgNPs with biochar significantly reduced VEGF and proinflammatory cytokine expression levels. Conclusions: Biochar and AgNPs may be novel treatments for bacteria and colorectal cancer cells, according to the current findings. [ABSTRACT FROM AUTHOR]

Abstract The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes. Liposomes were prepared and characterized for particle size and drug encapsulation and submitted to long-term stability tests. Cytotoxicity assays were performed in HeLa cells. Antineoplastic activity was investigated using the experimental sarcoma 180 tumor in Swiss albino mice. Encapsulation efficiency was 82.93 ± 0.04% and no significant changes were found with respect to particle size or pH after centrifugation and mechanical agitation tests. The in vitro results at concentration of 20 μg/mL indicated a considerable reduction in cell viability after treatment with encapsulated pyrimidine (75.91%). The in vivo assays using the compounds in encapsulated and free forms and 5-fluorouracil achieved tumor inhibition rates of 66.47 ± 26.8%, 50.46 ± 16.24% and 14.47 ± 9.22%, respectively. Mitotic counts demonstrated a greater reduction in the number of mitoses in animals treated with liposomal pyrimidine (32.15%) compared to those treated with the pyrimidine free (87.69%) and 5-fluorouracil (71.39%). This study demonstrated that the development of liposome formulations containing 4-amino-pyrimidine is a promising alternative for overcoming limitations related to the toxicity of current cancer treatment, ensuring greater therapeutic efficacy.

Cancer is considered one of the top global causes of death. Natural products have been used in oncology medicine either in crude form or by utilizing isolated secondary metabolites. Biologically active phytomolecules such as gallic acid and quercetin have confirmed antioxidant, anti-bacterial, and neoplastic properties. There is an agreement that microorganisms could mediate oncogenesis or alter the immune system. This research project aims to develop a novel formulation of co-loaded gallic acid and quercetin into nanoliposomes and investigate the efficacy of the free and combined agents against multiple cancerous cell lines and bacterial strains. Thin-film hydration technique was adopted to synthesize the nanocarriers. Particle characteristics were measured using a Zetasizer. The morphology of nanoliposomes was examined by scanning electron microscopy, Encapsulation efficiency and drug loading were evaluated using High-Performance Liquid Chromatography. Cytotoxicity was determined against Breast Cancer Cells MCF-7, Human Carcinoma Cells HT-29, and A549 Lung Cancer Cells. The antibacterial activities were evaluated against Acinetobacter baumannii, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Therapeutic formulas were categorized into groups: free gallic acid, free quercetin, free-mix, and their nano-counterparts. Findings revealed that drug loading capacity was 0.204 for the mix formula compared to 0.092 and 0.68 for free gallic acid and quercetin, respectively. Regarding the Zeta potential, the mix formula showed more amphiphilic charge than the free quercetin and free gallic acid formulas (P-values 0.003 and 0.002 receptively). On the contrary, no significant difference in polydispersity indices was reported. Lung cancerous cells were the most affected by the treatments. The best estimated IC50 values were observed in breast and lung cancer lines for the nano-gallic acid and co-loaded particles. The nano-quercetin formula exhibited the least cytotoxicity with an IC50 value of ≥200 μg/mL in both breast (MCF-7) and colorectal adenocarcinoma cell lines (HT-29) with no activity against the lung. A remarkable improvement in the efficacy of quercetin was measured after mixing it with gallic acid against the breast and lungs. The tested therapeutic agents exhibited antimicrobial activity against gram-positive bacteria. Nano-liposomes can either enhance or reduce the cytotoxicity activity of active compounds depending on the physical and chemical properties of drug-loaded and type of cancer cells.

Tumor refers to the neogrowth formed by the hyperplasia of local tissue cells under various tumor factors. Because this new creature mostly appears in a lump -like protrusions, also known as neoplasm. Relevant investigation shows that millions of new tumor cases and millions of tumor deaths occur every year. Although tumor treatments such as surgical resection, chemotherapy, radiotherapy, immunotherapy, endocrine therapy, and gene therapy can inhibit tumors to a certain extent, they also have a variety of shortcomings, such as poor drug targeting, expensive prices, serious toxic side effects, and limited efficacy. It is necessary to overcome the shortcomings of existing treatment strategies. Therefore, there are urgent needs for safe and effective new drugs to treat tumor. Marine polysaccharides have a wide range of sources, mainly including seaweed polysaccharides, marine animal polysaccharides and marine microbial polysaccharides. With the deepening of antitumor mechanism of marine polysaccharides, it is believed that marine polysaccharides may play an antitumor role by inhibiting tumor angiogenesis, inducing tumor cell apoptosis, scavenging free radicals, and activating the immune system. By referring to the literatures in recent 3 years, the antitumor effect and mechanism of marine polysaccharides were reviewed in order to provide reference for clinical medication.