TY - JOUR T1 - p53 Enhances Ascorbyl Stearate-induced G2/M Arrest of Human Ovarian Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 3927 LP - 3934 VL - 27 IS - 6B AU - K. AKHILENDER NAIDU AU - QUAN FANG AU - KAMATHAM A. NAIDU AU - JIN Q. CHENG AU - SANTO V. NICOSIA AU - DOMENICO COPPOLA Y1 - 2007/11/01 UR - http://ar.iiarjournals.org/content/27/6B/3927.abstract N2 - Background: 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 previously demonstrated that Asc-S inhibits ovarian carcinoma cell proliferation through modulation of the cell cycle. This study was designed to further elucidate the mechanisms underlying such regulation. Materials and Methods: Wild type p53-expressing cell lines (Ov2008 and C13) were used to evaluate the contributions of p53 to Asc-S-induced G2/M arrest. Cell cycle analysis was performed by flow cytometry. Variation of p53, p21, and GADD45 was evaluated by Western blot and RT-PCR. Knockdown of endogenous p53 was achieved by si-RNA. Results: The expression of p53 downstream genes, p21 and GADD45 was upregulated whereas 14-3-3σ was unaffected. Phosphorylation of Cdc2 at residue tyrosine-15 was also induced by Asc-S treatment. However, pSilencer-p53-siRNA only partially rescued the Asc-S induced G2/M arrest. Conclusion: These data show that the anti-proliferative activity of Asc-S on ovarian cancer cells is due in part to G2/M arrest modulated by a p53-dependent pathway. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -