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.
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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.)
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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
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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
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