Ascorbyl stearate induces G2/M cell cycle arrest in human ovarian epithelial cancer cells

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Ascorbyl stearate (Asc-S) is a synthetic ester of ascorbic acid that has been shown to significantly reduce the mutagenic effects of alkylating agents and hepatocarcinogenesis in vivo. We have previous demonstrated that Asc-S inhibits glioblastoma cells proliferation probably through cell cycle modulation (J Neuroncol 2001; 54:15-22). Here, we showed that Asc-S inhibits cell growth by induction of G2/M cell cycle arrest in human ovarian surface epithelial cancer cells. After Asc-S treatment, both wild type p53-expressing cell lines (Ov2008 and C13) and a mutated p53-expressing cell line (Ovcar-3) were arrested in G2/M phase of the cell cycle, suggesting that Asc-S can arrest ovarian cancer cells to G2/M checkpoint arrest via p53 dependent and independent pathways. The expression of p53 downstream genes, P21, GADD45 were upregulated whereas 14-3-3σ was unaffected. Phosphorylation of cdc2 at residue tyrosine 15 was also induced by Asc-S. Moreover, cdc25c was upregulated and redistributed as evaluated by immunofluorescence. This data suggest that anti-tumor activity of Asc-S is redulted from G2/M arrest in p53 dependent and independent pathways in human ovarian cancer cells.