Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane in the intestinal polyps of ApcMin/+ mice.
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-beta1 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.
Khor
Tin Oo
TO
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Hu
Rong
R
Shen
Guoxiang
G
Jeong
Woo-Sik
WS
Hebbar
Vidya
V
Chen
Chi
C
Xu
Changjiang
C
Nair
Sujit
S
Reddy
Bandaru
B
Chada
Kiran
K
Kong
Ah-Ng Tony
AN
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D017491:Genes, APC; D007417:Intestinal Polyps / Q000188:drug therapy* / Q000235:genetics; D017879:Isothiocyanates; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D013861:Thiocyanates / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D001093:Arachidonate 15-Lipoxygenase; D051546:Cyclooxygenase 2; C016766:sulforaphane