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The pharmaceutical industry has long focused on nature-derived biologically active compounds to address challenges in cancer treatment, particularly overcoming cancer cell resistance to programmed cell death, including apoptosis and ferroptosis. The cytotoxic effect of Amanita muscaria acetone extract on the JAR choriocarcinoma cell line was evaluated using MTT assay and analysis on two selected programmed cell death pathways. The putative ferroptotic effect was evaluated by measuring the main redox parameters and relative expression of key antiferroptotic genes. Our findings indicate that the IC50 of the acetone extract of A. muscaria was 168.96 (after 24 h) and 43.85 (after 72 h) mg/mL, inducing mainly a proapoptotic effect on choriocarcinoma cells. The extract also demonstrated an antiferroptotic effect. Both the proapoptotic and antiferroptotic effects were achieved regardless of the induction of oxidative stress._ This is the first report on A. muscaria acetone extract indicating proapoptotic and antiferroptotic effects on choriocarcinoma cells.

We examined potential biological activities of two taxa of freshwater algae, Cladophora glomerata and Vaucheria sp., from Serbia. The total phenolic and pigment contents, antioxidant potential, antimicrobial, antibiofilm activities, and cytotoxicity of the ethanol and acetone extracts were evaluated. The extracts were also subjected to Fourier transform infrared spectroscopy (FTIR) analysis. The levels of total phenolic compounds, chlorophylls a and b, and carotenoids varied based on both the algal taxa and the type of extracts. FTIR analysis showed the presence of lipids, unsaturated fatty acids, protein, carbohydrates, and phenols in the algal extracts. The extracts had moderate DPPH radical scavenging activity and lower reducing power compared with ascorbic acid. The antimicrobial activity expressed as minimum inhibitory concentrations ranged from 0.31 mg/mL to 10 mg/mL. The strains of Staphylococcus aureus and Bacillus cereus isolated from food samples, as well as S. aureus ATCC 25923, were the most sensitive. For the first time, the antibiofilm activity test revealed 98.7% inhibition of S. aureus biofilm formation. The extracts exhibited cytotoxic effects on choriocarcinoma JAR cells but without selectivity on normal fetal lung fibroblast MRC-5 cells. This is the first report on the biological activities of freshwater macroalgae from Serbia.

Medicinal plants have widely been used as a natural source of remedies for treating several diseases, including colorectal cancer. Ocimum minimum L. is a very important dietary plant used in traditional and modern medicine, due to its health beneficial effect realized by cytotoxic, proapoptotic, antioxidant/prooxidant, antiviral and antimicrobial activity. The biological activity of O. minimum flowers has been evaluated in HCT116 colorectal carcinoma cells through antiproliferative activity by MTT assay, pro-apoptotic activity by AO/EB and concentrations of redox status parameters (O2∙ and lipid peroxidation) by colorimetric methods. The protein expression of iNOS was analyzed by immunocytochemistry, while the antimigratory effect was measured by xCELLigence system. The treatment with O. minimum shows the antiproliferative, proapoptotic, impact on redox status parameters and antimigratory effect on HCT-116 cells. Based on obtained results, the pharmacological effect of O. minimum is evident against HCT-116 colorectal carcinoma cells, suggesting that this plant may be good start material for future anticancer therapy investigation.

In this study, the anticancer effect of Melittin was demonstrated through its antiproliferative and proapoptotic effects on HT-29 cells, as well as its ability to reverse multidrug resistance. Melittin directly affects the death receptor-dependent apoptotic pathway via increase of the Fas receptor protein expression, Caspase 8 gene expression and activity of Caspase 8. Results of decreased Caspase 9 gene and protein expression, and multi-fold increased expression of Bcl-2 gene suggest that mitochondria and the inner apoptotic pathway are not involved in the execution of Melittin induced apoptosis, as well as redox regulation of apoptosis based on decreased concentration of superoxide anion radicals and no effect glutathione levels. Specially significance of this work are results on ability of Melittin to modulate the metabolism and export system in cancer cells. Based on the increased expression of all the investigated genes related to the biotransformation process, it can be assumed that CYP1A1, CYP1B1, GSTP1 and MRP2 are involved in metabolism of Melittin in HT-29 cells. P-glycoprotein is associated with the occurrence of resistance in anticancer therapy, so its reduced gene and protein expression by Melittin represents significant result in terms of possible therapeutic application and examination. [ABSTRACT FROM AUTHOR]

The aim of this study was an investigation of pro-apoptotic activity of methanol extract from T. chamaedrys, a more detailed determination of the signal molecules activated in the process of apoptosis, and effects on mRNA expression of enzymes involved in biotransformation (CYP1A1 and GSTP1) and membrane transporter, MRP-2 in HCT-116 colorectal carcinoma cells. The results show pronounced proapoptotic activity of T. chamaedrys extract, due to activation of both extrinsic and intrinsic pathways. The death receptor associated signaling pathway was activated in HCT-116 following treatment by T. chamaedrys, via increased Fas receptor expression and activity of caspase 8. Activation of caspase 9 suggests that mitochondrial signalling also has an impact. The extract reduced mRNA expression of GSTP1 and MRP-2 genes, as one of the causes of multi drug resistance in cancer cells. Observed results offer the possibility for the use of T. chamaedrys extract in the context of cancer prevention and therapy.

Royal jelly is natural bee product, traditionally used in medicine for antitumor, anti-inflammatory, antioxidant, antibiotic and many other beneficial properties. The aim of this study was to determine biological effects of royal jelly samples originating from Serbia on normal human fibroblast (MRC-5) and colorectal cancer (HCT-116 and SW-480) cells. MTT cell viability assay was used to determine cytotoxic activity, and NBT test was used for determination of superoxide anion radical concentration. Parameters of cell energy status were determined using LDH and ATP colorimetric methods. Relative expression of mRNA of apoptosis and biotransformation genes was monitored by qPCR method. Royal jelly affected cell viability, caused oxidative stress appearance and elevated parameters of energy status in cancer cell lines. The relative expression of genes whose proteins are included in biotransformation of xenobiotics were changed with notable suppression of CYP1A1, while increased expression of apoptosis genes was noted in tested cell lines. Royal jelly demonstrated cell selective effect and could be prospective in anticancer therapy.

In this study, green synthesis of two derivatives of coumarin–hydroxybenzohydrazide, (E)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (C–HB1), and (E)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (C–HB2) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC50 values for C-HB1 and C-HB2 in relation to the DPPH radical are 6.4 and 2.5 μM, respectively, while they are 4.5 and 2.0 μM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH● follows HAT, while inactivation of ABTS+● follows SET-PT and HAT mechanisms. Additionally, coumarin–hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O2˙− concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the cytotoxic and proapoptotic activity of methanol extracts from Teucrium polium L. and T. montanum L. on immortalized cell lines of breast cancer (MDA-MB-231) and colorectal carcinoma (SW- 480). The cytotoxic activity was determined using MTT cell viability assay, where IC50 value was used as a parameter for cytotoxicity. The type of cell death was explored by fluorescence microscopy using acridine orange/ethidium bromide method. For determination apoptosis signal pathways expression of Fas receptor was monitored by immunofluorescence, while caspases 8 and 9 activity was analyzed, by colorimetric based assays. The results indicate that both plant extracts induced decrease of MDA-MB-231 and SW-480 cell viability, good cytotoxicity (IC50 values in range of 118.26 to 429.32 μg/ml, depends on type of cells and extracts, as well on treatment periods) and induced apoptosis, as a dominant type of cells death (6-11% of total cells). Investigated treatments led to increase in Fas receptor expression only in the case of T. montanum treatment on MDA-MB-231 cells. Additionaly, apoptosis was activated and realized via external pathway with the activation of internal apoptotic pathway mediated by caspases 8 i 9 in MDA-MB-231 cells while apoptosis occurred by caspase-independent pathway in SW- 480 cells. In conclusion, the results showed that the investigated methanol extract of Teucrium species showed good cytotoxic and proapoptotic activities, T. montanum expressed better activity, and the MDA-MB-231 cells were more sensitive to treatments.

Insect silk has been widely studied for its application in regenerative medicine. However, the data about Plodia interpunctella silk as a biomaterial and its anticancer properties are insufficient. Thus, the aim of this study was to investigate native silk as a substrate for growing normal human fibroblasts MRC-5, and test potential cytotoxic effects of the two silk extracts (with DMSO and Trypsin for sericin isolation) on HCT-116 colorectal carcinoma cells and MRC-5 fibroblasts as a control. Fifth-instar larval silk, collected for 15 and 30 days, was used for testing of proliferation and adhesion of MRC-5, 24 h and 72 h after seeding. Light- and fluorescence-microscope showed cell adhesion and spread on silk, as well as enhanced number of cells after 72 compared to 24 h and nonsignificant percentage of apoptotic cells on the silk. Although insoluble, P. interpunctella silk showed remarkable cytotoxic activity on HCT-116 cells, without significant cytotoxity on normal fibroblasts after 24 h and weak effects after 72 h. This study provides significant information about P. interpunctella silk as a potential biomaterial and shows the presence of some active constituents with anticancer properties, thus pointing to the possibility for exploitation of this worldwide pest insect in biomedical application. [ABSTRACT FROM AUTHOR]