Premium
3,3′‐Diindolylmethane Enhances the Efficacy of Butyrate in Colon Cancer Prevention through Down‐regulation of Survivin
Author(s) -
Bhatnagar Namrata,
Li Xia,
Chen Yue,
Zhou Xudong,
Garrett Scott H,
Guo Bin
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.940.4
Subject(s) - survivin , butyrate , cancer research , apoptosis , adenomatous polyposis coli , colorectal cancer , familial adenomatous polyposis , cancer prevention , cancer , sodium butyrate , medicine , chemistry , gene , biochemistry , fermentation
Butyrate is an inhibitor of histone deacetylase (HDAC) and has been extensively evaluated as a chemoprevention agent for colon cancer. We recently demonstrated that mutations in the adenomatous polyposis coli (APC) gene confer resistance to HDAC inhibitor‐induced apoptosis in colon cancers (Huang and Guo, Cancer Research, 66(18), 9245‐9251, 2006). Here we show that APC mutation rendered colon cancer cells resistant to butyrate‐induced apoptosis due to the failure of butyrate to down‐regulate survivin in these cells. Another cancer preventive agent, 3,3′‐Diindolylmethane (DIM), was identified to be able to down‐regulate survivin in colon cancers expressing mutant APC. Pre‐treatment with DIM enhanced butyrate‐induced apoptosis. Down‐regulation of survivin by DIM occurred at both transcription and post‐translation level through increased protein degradation. We further demonstrated that DIM was able to down‐regulate survivin and enhance the effects of butyrate in apoptosis induction and prevention of familial adenomatous polyposis in APC min/+ mice. Thus, the combination of DIM and butyrate is potentially an effective strategy for the prevention of colon cancer. This research was supported by Grants 1R03CA130062, 5R21CA111765 and 2P20RR015566 from the National Institutes of Health (NIH).