Juglone exerts antitumor effect in ovarian cancer cells.

Objective: 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 SKOV3 cells.

Methods: MTT assay was performed to examine juglone anti-proliferative effect. Cell cycle and apoptosis were studied using flow cytometry in juglone-treated SKOV3 cells. To investigate molecular mechanism of cell cycle and apoptosis, protein expression levels were measured by Western blot analysis of cyclin D1, Bcl-2, Bax, cytochrome c, caspase-9 and caspase-3. To investigate the motility of juglone-treated SKOV3 cell, Matrigel invasion assay was employed to characterize cell invasion. Also, matrix metalloproteinase-2 (MMP-2) expression levels were detected by western blot.

Results: Juglone significantly inhibited SKOV3 cell proliferation as shown by G0/G1 phase arrest, and this effect was mediated by inactivation of cyclin D1 protein (P<0.05). Juglone induced apoptosis in SKOV3 cell which was accompanied by caspase-9 and caspase-3 activation (P<0.05). Juglone decreased Bcl-2 levels and increased Bax and cytochrome c (Cyt c) levels (P<0.05). Juglone sufficiently inhibited invasion while evidently decreased MMP-2 expression (P<0.05).

Conclusions: The results suggest that juglone could probably induce apoptosis through mitochondrial pathway and restrained cell invasiveness by decreasing MMP expression.