This study aimed at evaluating whether morin (a natural flavonoid and a known inhibitor of NF-κB) can sensitize ovarian cancer cells to cisplatin by decreasing the expression of galectin-3, which is an anti-apoptotic protein regulated by NF-κB transcription factor.

Purpose Assessment of miR-424-3p mimic capability to sensitize SK-OV-3 and TOV-21G ovarian cancer cells to cisplatin by decreasing the expression of galectin-3, which is an anti-apoptotic protein overexpressed in ovarian cancer and associated with resistance to chemotherapy. Methods We performed a reverse transfection of miR-424-3p mimic into SK-OV-3 and TOV-21G ovarian cancer cells, followed by Real Time™ RT-PCR analysis of the expression of miR-424-3p and galectin-3 mRNA as well as ELISA assay for galectin-3 protein level. Next, we studied the viability (XTT assay), proliferation (EdU incorporation assay), and apoptosis (ELISA assay) of the both cell lines transfected with the mimic and treated with cisplatin. Results We demonstrated that miR-424-3p mimic effectively transfects into SK-OV-3 and TOV-21G ovarian cancer cells in which it significantly suppresses the expression of galectin-3 at the protein level, but not at the mRNA level. Reverse transfection of both cell lines with the mimic, followed by treatment with cisplatin, resulted in a reduction in cell viability and proliferation as well as an increase in the induction of apoptosis. Conclusions MiR-424-3p mimic sensitizes SK-OV-3 and TOV-21G ovarian cancer cells to cisplatin by decreasing the expression of galectin-3.

The influence of morin hydrate on changes of proliferative, metastatic, and adhesive potential of human ovarian cancer cells concerning the influence of decitabine, and decitabine with trichostatin A, and in comparison to untreated cells, were analyzed. The effect of morin hydrate, decitabine, and trichostatin A were examined in A2780 and SKOV-3 ovarian cancer cell lines using MTS assay, clonogenic assay, adhesion to endothelial HMEC-1 cells, transwell migration assay and cell cycle analysis. The expression level of epithelial to mesenchymal transition (EMT) markers was quantified using PCR Array in relation to the level of global methylation determined with Methylated DNA Quantification Kit. We observed statistically significant inhibition of adhesive and migratory potential of both cell lines and the accumulation of G0/G1 phase A2780 cells after treatment with morin hydrate. Our studies confirmed the influence of morin hydrate on down-regulation of genes considered as up-regulated during EMT, and up-regulation of some genes considered as down-regulated during EMT in A2780 and SKOV-3 cells. Phenotypic changes were associated with molecular changes in cells, eg. decrease of the expression level of genes associated with adhesion, and an increase of genes down-regulated during EMT, after morin hydrate treatment in comparison to untreated control cells in both cell lines, were observed.

Summary: Reactive oxygen species (ROS) are critically involved in the action of anticancer agents. In this study, we investigated the role of ROS in the anticancer mechanism of new aminoalkanol derivatives of xanthone. Most xanthones used in the study displayed significant pro-oxidant effects similar to those of gambogic acid, one of the most active anticancer xanthones. The pro-oxidant activity of our xanthones was shown both directly (by determination of ROS induction, effects on the levels of intracellular antioxidants, and expression of antioxidant enzymes) and indirectly by demonstrating that the overexpression of manganese superoxide dismutase decreases ROS-mediated cell senescence. We also observed that mitochondrial dysfunction and cellular apoptosis enhancement correlated with xanthone-induced oxidative stress. Finally, we showed that the use of the antioxidant N-acetyl-L-cysteine partly reversed these effects of aminoalkanol xanthones. Our results demonstrated that novel aminoalkanol xanthones mediated their anticancer activity primarily through ROS elevation and enhanced oxidative stress, which led to mitochondrial cell death stimulation; this mechanism was similar to the activity of gambogic acid.

Natural xanthones are a large group of compounds from which promising anticancer properties could be further developed by chemical modifications. This study aimed to investigate the influence of four novel xanthone derivatives based on a naturally occurring xanthone skeleton on the invasiveness of colon cancer cells in vitro. First, the concentrations required to inhibit growth of three colorectal cancer cell lines to 50% (GI₅₀) of all the studied compounds, as well as the natural xanthones used as a reference (gambogic acid and α-mangostin), have been established (MTS reduction test). Next, the assays determining several aspects of the GI₂₅ xanthones influence on colorectal cancer cells, including cytotoxicity, migration and invasion potential, interaction with extracellular matrix and endothelial cells, as well as expression of selected invasiveness related genes have been performed. Our results demonstrate that these novel xanthone derivatives impair colorectal cancer proliferation, motility, adhesion to extracellular matrix and to endothelial cells, and also induce apoptosis and cell death. Moreover, their activity is comparable to cisplatin and 5-fluorouracil, used as reference compounds. Conducted research indicates our compounds for further research and development as novel drugs in colorectal cancer treatment.