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

doi:10.1038/nm1197-1233

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

Department of Statistics

Research output: Contribution to journal › Article › peer-review

337 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 language	English
Pages (from-to)	1233-1241
Number of pages	9
Journal	Nature Medicine
Volume	3
Issue number	11
DOIs	https://doi.org/10.1038/nm1197-1233
Publication status	Published - 1997 Nov

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nm1197-1233

Cite this

@article{61685ab9de5a4c4c8599790a13906d0f,

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

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.",

author = "Rebecca Chinery and Brockman, {Jeffrey A.} and Peeler, {Mark O.} and Yu Shyr and Beauchamp, {R. Daniel} and Coffey, {Robert J.}",

year = "1997",

month = nov,

doi = "10.1038/nm1197-1233",

language = "English",

volume = "3",

pages = "1233--1241",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer

T2 - A p53-independent induction of p21(WAF1/CIP1) via C/EBPβ

AU - Chinery, Rebecca

AU - Brockman, Jeffrey A.

AU - Peeler, Mark O.

AU - Shyr, Yu

AU - Beauchamp, R. Daniel

AU - Coffey, Robert J.

PY - 1997/11

Y1 - 1997/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030663670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030663670&partnerID=8YFLogxK

U2 - 10.1038/nm1197-1233

DO - 10.1038/nm1197-1233

M3 - Article

C2 - 9359698

AN - SCOPUS:0030663670

SN - 1078-8956

VL - 3

SP - 1233

EP - 1241

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this