Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: A p53-independent induction of p21(WAF1/CIP1) via C/EBPβ

Rebecca Chinery, Jeffrey A. Brockman, Mark O. Peeler, Yu Shyr, R. Daniel Beauchamp, Robert J. Coffey

研究成果: Article同行評審

334 引文 斯高帕斯(Scopus)

摘要

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Five-fluorouracil (5FU) remains the single most effective treatment for advanced disease, despite a response rate of only 20%. Herein, we show that the antioxidants pyrrolidinedithiocarbamate and vitamin E induce apoptosis in CRC cells. This effect is mediated by induction of p21(WAF1/CIP1), a powerful inhibitor of the cell cycle, through a mechanism involving C/EBPβ (a member of the CCAAT/enhancer binding protein family of transcription factors), independent of p53. Antioxidants significantly enhance CRC tumor growth inhibition by cytotoxic chemotherapy in vitro (5FU and doxorubicin) and in vivo (5FD). Thus, chemotherapeutic agents administered in the presence of antioxidants may provide a novel therapy for colorectal cancer.

原文English
頁(從 - 到)1233-1241
頁數9
期刊Nature Medicine
3
發行號11
DOIs
出版狀態Published - 1997 十一月

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)

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