Indole-3-carbinol and prostate cancer.
Epidemiological and dietary studies have revealed an association between high dietary intake of cruciferous vegetables and decreased prostate cancer risk. Our studies have shown that indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its in vivo dimeric product 3,3'-diindolylmethane (DIM) upregulate the expression of phase I and phase II enzymes, suggesting increased capacity for detoxification and inhibition of carcinogens. Studies from our laboratory and others have found that I3C can induce G1 cell-cycle arrest and apoptosis in prostate cancer cells. In addition, we found, by microarray gene expression profiling, that I3C and DIM regulate many genes that are important for the control of cell cycle, cell proliferation, signal transduction, and other cellular processes, suggesting the pleiotropic effects of I3C and DIM on prostate cancer cells. We recently found that I3C functions as an inhibitor of Akt and nuclear factor kappaB (NF-kappaB), which play important roles in cell survival and which are believed to be potential targets in cancer therapy. Studies have already shown that the inactivation of Akt and NF-kappaB is responsible for chemosensitization of chemoresistant cancer cells. Because there is no effective treatment strategy for hormone-dependent and, most importantly, hormone-independent and metastatic prostate cancer, our strategies to sensitize prostate cancer cells to a chemotherapeutic agent by I3C and DIM is a novel breakthrough that could be used for devising novel therapies for prostate cancer. In conclusion, the results from our laboratory and from others provide ample evidence for the benefit of I3C and DIM for the prevention and the treatment of prostate cancer.
Sarkar
Fazlul H
FH
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA. fsarkar@med.wayne.edu
Li
Yiwei
Y
D017209:Apoptosis / Q000187:drug effects; D019607:Brassicaceae / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects
D007211:Indoles; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C016517:indole-3-carbinol; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt