Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

Wu,Jiang; Ji,Fang; Di,Wen; Chen,Hongduo; Wan,Yinsheng

doi:10.3892/ol.2011.286

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

Authors:
- Jiang Wu
- Fang Ji
- Wen Di
- Hongduo Chen
- Yinsheng Wan
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Affiliations: Department of Biology Providence College, Providence, RI 02918-0001, USA, Department of Obstetrics and Gynecology, Renji Hospital of Shanghai Jiaotong University Medical School, Shanghai 200001, P.R. China, Department of Biology Providence College, Providence, RI 02918-0001, USA
Published online on: March 21, 2011 https://doi.org/10.3892/ol.2011.286
Pages: 543-547

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Abstract

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

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