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

Research output: Contribution to journalArticlepeer-review

329 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1233-1241
Number of pages9
JournalNature Medicine
Volume3
Issue number11
DOIs
Publication statusPublished - 1997 Nov

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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