Evidence of a novel antiapoptotic factor: role of inhibitor of differentiation or DNA binding (Id-1) in anticancer drug-induced apoptosis.

Abstract

Id-1 (inhibitor of differentiation or DNA binding), a member of the basic helix-loop-helix transcription factor family, is up-regulated in many types of human cancer and its expression levels are correlated with poor treatment outcome and shorter survival. In this study, we provided evidence to suggest that Id-1 is a universal survival factor that plays a key role in protection against anticancer drug-induced apoptosis. Using nine anticancer drugs and five cancer cell lines derived from nasopharyngeal carcinoma (CNE1), cervical carcinoma (HeLa), breast cancer (MCF7), hepatocarcinoma (Huh7) and prostate cancer (PC3), we found that down-regulation of Id-1 expression at both transcriptional and protein levels was associated with increased apoptosis rates and increased cleaved PARP after exposure to all anticancer agents. Treatment with a caspase 9 inhibitor, Z-LEHD-FMK, protected cancer cells from drug-induced PARP cleavage. However, overexpression of Id-1 in a p53 mutated cell line, CNE1, was able to suppress PARP cleavage in response to all anticancer drugs examined. In contrast, down-regulation of Id-1 through small RNA technology in CNE1 cells led to increased sensitivity to all six types of chemotherapeutic drugs. Our results demonstrate that Id-1 may be a general negative regulator of anticancer drug-induced apoptosis and suggest a novel therapeutic target in inducing chemosensitization in cancer cells. Our evidence also provides a possible underlying mechanism responsible for the positive role of Id-1 in the progression of human cancer.

• Authors: Xiaomeng Zhang, Ming-Tat Ling, Yong-Chuan Wong, Xianghong Wang
• Journal: Cancer science (Cancer Sci) Vol. 98 Issue 3 Pg. 308-14 (Mar 2007) ISSN: 1347-9032 [Print] England
• PMID: 17214747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Inhibitor of Differentiation Protein 1
• Mechlorethamine
• Mitomycin
• Vincristine
• Etoposide
• Doxorubicin
• Catechin
• epigallocatechin gallate
• Paclitaxel
• Cisplatin
• Methotrexate

Topics

• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Breast Neoplasms (pathology)
• Carcinoma, Hepatocellular (pathology)
• Catechin (analogs & derivatives, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (therapeutic use)
• Down-Regulation
• Doxorubicin (therapeutic use)
• Etoposide (therapeutic use)
• Female
• HeLa Cells
• Humans
• Inhibitor of Differentiation Protein 1 (metabolism, physiology)
• Liver Neoplasms (pathology)
• Male
• Mechlorethamine (therapeutic use)
• Methotrexate (therapeutic use)
• Mitomycin (therapeutic use)
• Nasopharyngeal Neoplasms (pathology)
• Paclitaxel (therapeutic use)
• Prostatic Neoplasms (pathology)
• Vincristine (therapeutic use)