Induction of p27(kip1) by 2,4,3',5'- tetramethoxystilbene is regulated by protein phosphatase 2A-dependent Akt dephosphorylation in PC-3 prostate cancer cells.
trans-Stilbenes induce cytochrome P450 1B1 (CYP1B1) inhibition and cell death. 2,4,3',5' tetramethoxystilbene (TMS), a synthetic trans-stilbene analog, induced apoptotic cell death in PC-3 prostate cancer cells, as evidenced by a decrease in the mitochondrial membrane potential. TMS-induced apoptosis was associated with an increase in the level of cell cycle inhibitor, p27(kip1), through reduction of Akt-mediated Skp2 expression. TMS-induced activation of protein phosphatase 2A (PP2A) inhibited Akt phosphorylation and p27(kip1) expression, indicating that PP2A is involved in the induction of p27(kip1) via Akt inhibition. These results suggest that TMS may inhibit the cell cycle through induction of p27(kip1), leading to apoptotic cell death in PC-3 prostate cancer cells.
Kim
Sang Woo
SW
College of Pharmcay, Chung-Ang University, Seoul, Korea.
Jung
Hong Keun
HK
Kim
Mie Young
MY
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection
C440850:2,4,3',5'-tetramethoxystilbene; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; D013267:Stilbenes; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D051058:Oncogene Protein v-akt; D054648:Protein Phosphatase 2