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| Content Provider | PubMed Central |
|---|---|
| Author | Khan, Naghma Afaq, Farrukh Syed, Deeba N. Mukhtar, Hasan |
| Copyright Year | 2008 |
| Abstract | Novel dietary agents for prevention and therapy of prostate cancer (PCa) are desired. The aim of this study was to determine the effect of fisetin, a tetrahydroxyflavone, on inhibition of cell growth and induction of apoptosis in human PCa cells. Treatment of fisetin (10–60 μM, 48 h) was found to result in a decrease in the viability of LNCaP, CWR22Rυ1 and PC-3 cells but had only minimal effects on normal prostate epithelial cells as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide assay. Treatment of LNCaP cells with fisetin also resulted in G1-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser473 and Thr308. There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9. Pretreatment of cells with caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced activation of caspases. These data provide the first evidence that fisetin could be developed as an agent against PCa. |
| Related Links | http://dx.doi.org/10.1093/carcin/bgn078 |
| Ending Page | 1056 |
| Page Count | 8 |
| Starting Page | 1049 |
| File Format | |
| ISSN | 01433334 |
| e-ISSN | 14602180 |
| Journal | Carcinogenesis |
| Issue Number | 5 |
| Volume Number | 29 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2008-05-01 |
| Access Restriction | Open |
| Rights Holder | Oxford University Press |
| Subject Keyword | Cancer Research Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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