Inhibitory Effect Of Snake Venom Toxin From On Hormone-Refractory Human Prostate Cancer Cell Growth

Main Category: Urology / Nephrology
Also Included In: Prostate / Prostate Cancer;  Cancer / Oncology
Article Date: 05 Mar 2007 - 0:00 PDT

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UroToday.com- Snake venom as therapeutic treatment of cancer? This certainly sounds unusual, but Dr. Son and colleagues report on the effectiveness of the snake venom toxin (SVT) Vipera lebetina turanica in the inhibition of androgen-independent prostate cancer (AICAP) in the February 2007 issue of Molecular Cancer Therapeutics.

The molecular focus of this report was on nuclear factor B (NF-B), an anti-apoptotic transcriptional factor that is constitutively activated in AICAP cell lines. The scientists showed that SVT inhibited growth of AICAP cells lines PC-3 and DU145 with IC50's of 1.7 and 1.8ug/mL, respectively. This exceeded the IC50 in LNCaP, androgen-sensitive cells (9.1ug/mL). With increasing concentrations of SVT, the number of cells distributed in the S phase of the cell cycle decreased significantly compare with cells in other phases.

To investigate whether SVT can inactivate NF-B and thus cause cells to undergo apoptosis, PC-3 cells treated with SVT for 24 hours were assessed. The SBR interacts with NF-B signal molecules by a protein-protein interaction with the cysteine residues in the NF-B molecules. Culturing the cells with SVT reduced the constitutive activation of NF-B. Interaction between SVT and mutant gene constructs was suggestive that the cysteine residues are the targets of SVT in the NF-B molecule. Expression of cell cycle regulatory proteins was also altered in the SVT treated cells with decreased expression of G2-M phase regulation protein cyclin B1 and proteins regulating G1 phase in the cells. The increase of apoptotic action was confirmed by the induction of caspase-3 and -9 activations by SVT.

These novel findings suggest that SVT can inhibit the growth of AICAP through the induction of cell death.

Dong Ju Son, Mi Hee Park, Sang Jin Chae, Soon Ok Moon, Jae Woong Lee, Ho Sueb Song, Dong Cheul Moon, Sang Sun Kang, Young Ee Kwon, and Jin Tae Hong
Mol Cancer Ther 2007; 6:675-683.

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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