A potential new drug for advanced prostate cancer

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Something to watch for further developments.

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Jon in Nevada

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Novel Inhibitor of the Growth and Invasion of Hormone-Refractory Prostate Cancer - Abstract Thursday, 13 November 2008

Aziz MH, Dreckschmidt NE, Verma AKDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53792, USA.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Hormone-refractory invasive PCa is the end stage and accounts for the majority of PCa patient deaths.

We present here that plumbagin (PL), a quinoid constituent isolated from the root of the medicinal plant Plumbago zeylanica L., may be a potential novel agent in the control of hormone-refractory PCa.

Specific observations are the findings that PL inhibited PCa cell invasion and selectively induced apoptosis in PCa cells but not in immortalized nontumorigenic prostate epithelial RWPE-1 cells. In addition, i.p. administration of PL (2 mg/kg body weight), beginning 3 days after ectopic implantation of hormone-refractory DU145 PCa cells, delayed tumor growth by 3 weeks and reduced both tumor weight and volume by 90%.

Discontinuation of PL treatment in PL-treated mice for as long as 4 weeks did not result in progression of tumor growth. PL, at concentrations as low as 5 micromol/L, inhibited in both cultured PCa cells and DU145 xenografts (a) the expression of protein kinase Cepsilon (PKCepsilon), phosphatidylinositol 3-kinase, phosphorylated AKT, phosphorylated Janus-activated kinase-2, and phosphorylated signal transducer and activator of transcription 3 (Stat3); ( the DNA-binding activity of transcription factors activator protein-1, nuclear factor-kappaB, and Stat3; and © Bcl-xL, cdc25A, and cyclooxygenase-2 expression.

The results indicate for the first time, using both in vitro and in vivo preclinical models, that PL inhibits the growth and invasion of PCa. PL inhibits multiple molecular targets including PKCepsilon, a predictive biomarker of PCa aggressiveness. PL may be a novel agent for therapy of hormone-refractory PCa.

Reference: Cancer Res. 2008 Nov 1;68(21):9024-32. doi:10.1158/0008-5472.CAN-08-2494PubMed Abstract PMID:18974148Get movies delivered to your mailbox. One month free from blockbuster.com