Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation: effects on 12-LOX and Rb protein phosphorylation - PubMed (original) (raw)
doi: 10.4161/cbt.6.2.3624. Epub 2007 Feb 25.
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- PMID: 17218785
- DOI: 10.4161/cbt.6.2.3624
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Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation: effects on 12-LOX and Rb protein phosphorylation
Peiying Yang et al. Cancer Biol Ther. 2007 Feb.
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Abstract
The multiherb anti-inflammatory product Zyflamend was investigated for its antiproliferative effects on PC3 human prostate cancer cells and eicosanoid metabolism in this prostate cancer cell line. Zyflamend produced a concentration-dependent inhibition of cloned COX-1, COX-2, and 5-LOX enzyme activities, with inhibition of 5-HETE production being greater than that of PGE(2) formation. Applied to intact PC3 cells, Zyflamend was found to be most potent against 12-LOX, followed by 5-LOX and then COX activities. The concentration-dependent inhibition of PC3 cell proliferation was associated with a selective G(2)/M arrest of the cell cycle and induction of apoptosis, as evidenced by flow cytometric staining of PC3 cells with annexin V. Zyflamend also produced a concentration-dependent down-regulation of 5-LOX and 12-LOX expression. Determination of cell signal transduction proteins demonstrated that Zyflamend produced an increase in p21 phosphorylation but down-regulated phosphorylation of retinoblastoma (Rb) protein. The decrease in pRb protein was shown to be due to 12-LOX inhibition and a decline in 12-HETE levels in the cells. Replenishing 12-HETE in Zyflamend-treated cells overcame the ability of this multiple herb product to inhibit cell proliferation, and concordantly, 12-HETE blocked Zyflamend's ability to down-regulate phosphorylation of Rb protein. We conclude that the effective control of human prostate cancer cell proliferation with Zyflamend is multi-mechanistic but, in part, involves regulation of aberrant tumor cell eicosanoid metabolism, especially on 5- and 12-LOX, as well as restoration of Rb tumor suppressor protein function through regulation of its phosphorylation status.
Comment in
- Inhibition of lipoxygenase activity: implications for the treatment and chemoprevention of prostate cancer.
Nelson MA. Nelson MA. Cancer Biol Ther. 2007 Feb;6(2):237. doi: 10.4161/cbt.6.2.4120. Epub 2007 Feb 8. Cancer Biol Ther. 2007. PMID: 17387265 No abstract available.
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