Premium
Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane in the intestinal polyps of ApcMin/+ mice
Author(s) -
Khor Tin Oo,
Hu Rong,
Shen Guoxiang,
Jeong WooSik,
Hebbar Vidya,
Chen Chi,
Xu Changjiang,
Nair Sujit,
Reddy Bandaru,
Chada Kiran,
Kong AhNg Tony
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.522
Subject(s) - sulforaphane , isothiocyanate , cancer research , carcinogenesis , cell growth , biology , wnt signaling pathway , cancer , apoptosis , cyp1b1 , cyclin d1 , gene , pharmacology , cell cycle , genetics , biochemistry , enzyme , cytochrome p450
Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed vegetables. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN could also suppress the growth of intestinal polyps in the ApcMin/+ mouse. In the present study, the acute effect of SFN on the gene expression profile in small intestinal polyps of ApcMin/+ mice using Affymetrix microarray was performed. SFN is a strong inducer for phase II drug metabolizing enzymes, which is believed to contribute to its chemopreventive properties. However, the results show that genes involved in apoptosis, cell growth and maintenance rather than the predicted phase II genes were modulated. The proapoptotic genes including MBD4, TNFR‐7 and TNF (ligand)‐11 were up‐regulated while pro‐survival genes including cyclin‐D2, integrin‐ β 1 and Wnt‐9A were down‐regulated. Interestingly, two genes potentially involved in colorectal carcinogenesis, 15‐LOX and COX‐2 were found to be increased and decreased, respectively. In conclusion, the results show, for the first time, that chemopreventive agents such as SFN regulate different set of genes involving apoptosis, cell growth/maintenance and inflammation in the small intestinal polyps of ApcMin/+ mice, which could contribute to the overall chemopreventive pharmacological effects. Copyright © 2006 John Wiley & Sons, Ltd.