P53 enhances ascorbyl stearate-induced G2/M arrest of human ovarian cancer cells.

Abstract

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 siRNA.

RESULTS:

The expression of p53 downstream genes, p21 and GADD45 was upregulated whereas 14-3-3sigma 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.

• Authors: K Akhilender Naidu, Quan Fang, Kamatham A Naidu, Jin Q Cheng, Santo V Nicosia, Domenico Coppola
• Journal: Anticancer research (Anticancer Res) 2007 Nov-Dec Vol. 27 Issue 6B Pg. 3927-34 ISSN: 0250-7005 [Print] Greece
• PMID: 18225552 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CDKN1A protein, human
• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p21
• GADD45A protein, human
• Nuclear Proteins
• RNA, Small Interfering
• TP53 protein, human
• Tumor Suppressor Protein p53
• ascorbyl monostearate
• Ascorbic Acid

Topics

• Ascorbic Acid (analogs & derivatives, pharmacology)
• Cell Cycle Proteins (biosynthesis, genetics)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis, genetics)
• Female
• G2 Phase (drug effects)
• Humans
• Nuclear Proteins (biosynthesis, genetics)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• RNA, Small Interfering (genetics)
• Tumor Suppressor Protein p53 (antagonists & inhibitors, biosynthesis, genetics)
• Up-Regulation