RT Journal Article
SR Electronic
T1 p53 Enhances Ascorbyl Stearate-induced G2/M Arrest of Human Ovarian Cancer Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3927
OP 3934
VO 27
IS 6B
A1 NAIDU, K. AKHILENDER
A1 FANG, QUAN
A1 NAIDU, KAMATHAM A.
A1 CHENG, JIN Q.
A1 NICOSIA, SANTO V.
A1 COPPOLA, DOMENICO
YR 2007
UL http://ar.iiarjournals.org/content/27/6B/3927.abstract
AB 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