The grape component piceatannol induces apoptosis in DU145 human prostate cancer cells via the activation of extrinsic and intrinsic pathways.
Piceatannol (trans-3,4,3',5'-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 micromol/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.
Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Republic of Korea.
Eun Ji
EJ
Kim
Heesook
H
Park
So Young
SY
Park
Jong-Gab
JG
Jun
Jung Han Yoon
JH
Park
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D027843:Vitis / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D010936:Plant Extracts; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases