Abstract
PurposeThis 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.MethodsTo assess the possibility of augmentation the activity of cisplatin by morin, we studied the separate and the combined effect of morin and cisplatin on viability, proliferation, and apoptosis of TOV-21G (cisplatin-sensitive) and SK-OV-3 (cisplatin-resistant) ovarian cancer cells. We also analysed the effect of morin and cisplatin on galectin-3 expression at the mRNA and protein levels.ResultsWe demonstrated that morin possess antitumor activity against TOV-21G and SK-OV-3 ovarian cancer cells by reducing cell viability and proliferation as well as increasing the induction of apoptosis. Co-treatment of the cells with selected concentrations of morin and cisplatin, accordingly to specific treatment approaches, reveals a synergism, which leads to sensitization of the cells to cisplatin. During this sensitization, morin significantly reduces the expression of galectin-3 at the mRNA and protein level, regardless of the presence of cisplatin.ConclusionsMorin sensitizes TOV-21G and SK-OV-3 ovarian cancer cells to cisplatin, what is associated with a decrease of the expression of galectin-3.
Highlights
Ovarian cancer is one of the leading causes of cancer death in female worldwide [1,2,3,4,5], despite the fact that it accounts for only 3% of all cancer in women [6]
Morin enhances the cytotoxicity of cisplatin against ovarian cancer cells To investigate whether morin can modulate the cytotoxic effect of cisplatin against ovarian cancer cells, we first evaluated the viability of TOV-21G and SK-OV-3 cells treated with cisplatin (3.125–200 μM) for 24 h or morin (50–400 μM) for 24 h and 48 h
Morin treatment revealed its cytotoxic effect in a dose- and time-dependent manner (TOV-21G p < 0.01; SK-OV-3 p < 0.001; Fig. 1b, c), but there were no significant differences between IC50 values obtained for both cell lines during 24-h treatment (IC50 = 392.59 ± 22.55 μM and 397.85 ± 18.54 μM for TOV21G and SK-OV-3, respectively; Fig. 1d) or 48-h treatment (IC50 = 228.52 ± 7.77 μM and 239.09 ± 16.59 μM for TOV21G and SK-OV-3, respectively; Fig. 1d)
Summary
Ovarian cancer is one of the leading causes of cancer death in female worldwide [1,2,3,4,5], despite the fact that it accounts for only 3% of all cancer in women [6]. Cytoreductive surgery followed by treatment with combination of cisplatin (or carboplatin) and paclitaxel is currently the standard method for ovarian cancer therapy [3,4,5]. The two main reasons of high mortality in ovarian cancer are lack of early symptoms and platinum resistance of cancer cells (intrinsic or acquired). The anticancer effect of cisplatin (cisdiamminedichloroplatinum(II)) involves active uptake into cells, followed by forming DNA adducts, that cause single or double-strand DNA breaks. The DNA damages result in DNA replication and cell cycle arresting, as well as activation of the cellular apoptosis [7, 8]. One of its underlying factors is an impairment of apoptosis, involving the altered expression of proteins such as BCL-2 family members and defects in several signal transducers, including NF-κB [9, 10]. It is reported that NF-κB can influence the expression of BCL-2 proteins and that constitutive
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