Juglone exerts antitumor effect in ovarian cancer cells

Objective(s): Juglone is isolated from many species of the Juglandaceae family and used as an anti-viral, anti-bacterial, and anti-tumor therapeutic. Here, we evaluated juglone-induced antitumor effect in ovarian cancer SKOV۳ cells. Materials and Methods: MTT assay was performed to examine juglone anti-proliferative effect. Cell cycle and apoptosis were studied using flow cytometry in juglone-treated SKOV۳ cells. To investigate molecular mechanism of cell cycle and apoptosis, protein expression levels were measured by Western blot analysis of cyclin D۱, Bcl-۲, Bax, cytochrome c, caspase-۹ and caspase-۳. To investigate the motility of juglone-treated SKOV۳ cell, Matrigel invasion assay was employed to characterize cell invasion. Also, matrix metalloproteinase-۲ (MMP-۲) expression levels were detected by western blot. Results:Juglone significantly inhibited SKOV۳ cell proliferation as shown by G۰/G۱ phase arrest, and this effect was mediated by inactivation of cyclin D۱ protein (P<۰.۰۵). Juglone induced apoptosis in SKOV۳ cell which was accompanied by caspase-۹ and caspase-۳ activation (P<۰.۰۵). Juglone decreased Bcl-۲ levels and increased Bax and cytochrome c (Cyt c) levels(P<۰.۰۵). Juglone sufficiently inhibited invasion while evidently decreased MMP-۲ expression (P<۰.۰۵). Conclusion:The results suggest that juglone could probably induce apoptosis through mitochondrial pathway and restrained cell invasiveness by decreasing MMP expression.

کلیدواژه ها:

Apoptosis ، Cell Cycle Arrest ، Invasion ، Juglone ، Ovarian cancer