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.
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: Cheng-Xiong Xu; Meng Xu; Lei Tan; Hua Yang; Jennifer Permuth-Wey; Patricia A Kruk; Robert M Wenham; Santo V Nicosia; Johnathan M Lancaster; Thomas A Sellers; Jin Q Cheng Journal: J Biol Chem Date: 2012-08-27 Impact factor: 5.157
Authors: Laura E Pascal; Yao Wang; Mingming Zhong; Dan Wang; Anish Bhaswanth Chakka; Zhenyu Yang; Feng Li; Qiong Song; Lora H Rigatti; Srilakshmi Chaparala; Uma Chandran; Anil V Parwani; Zhou Wang Journal: Neoplasia Date: 2018-03-06 Impact factor: 5.715