Journal
JOURNAL OF MEDICINAL FOOD
Volume 12, Issue 5, Pages 943-951Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/jmf.2008.1341
Keywords
Bcl-2 proteins; caspases; cytochrome c; mitochondrial membrane permeability
Funding
- Korean Government (Ministry of Education, Science and Technology) [R01-2007-000-20164-0]
- Korea Science and Engineering Foundation
- Ministry of Education, Science and Technology, Republic of Korea
- National Research Foundation of Korea [R01-2007-000-20164-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Piceatannol (trans-3,4,30,50-tetrahydroxystilbene) is a polyphenol that is found in grapes, red wine, Rheum undulatum, and the seeds of Euphorbia lagascae. It has been previously reported that piceatannol inhibits the proliferation of a variety of cancer cell types. In the present study, we assessed the effects of piceatannol on the growth of androgen-insensitive DU145 prostate cancer cells at concentrations of 1-10 mu mol/L. Piceatannol reduced the viable numbers and increased the numbers of apoptotic DU145 cells in a dose-dependent manner. Western blot analysis revealed that piceatannol increased the protein levels of cleaved caspase-8, -9, -7, and -3 and cleaved poly(ADP-ribose) polymerase (PARP). Piceatannol increased mitochondrial membrane permeability and cytochrome c release from the mitochondria to the cytosol. Piceatannol induced an increase in the levels of truncated Bid, Bax, Bik, Bok, and Fas but caused a decrease in the levels of Mcl-1 and Bcl-xL. Caspase-8 and -9 inhibitors mitigated piceatannol-induced apoptosis. The caspase-8 inhibitor suppressed the piceatannol-induced cleavage of Bid, caspase-3, and PARP. These results indicate that piceatannol induces apoptosis via the activation of the death receptor and mitochondrial-dependent pathways in prostate cancer cells.
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