This seems unusual, but Dr. Son and colleagues report on the effectiveness of the toxin from snake venom (SVT) Vipera lebetina turanica in the inhibition of androgen-independent prostate cancer (AICAP) in the journal Molecular Cancer Therapeutics.
The molecular emphasis of this report was the nuclear factor KB (NF-KB), an anti-apoptotic transcription factor that is constitutively activated in cell lines AICAP. The scientists showed that SVT inhibited growth AICAP cell lines PC-3 and DU145 with IC50 of 1.8ug/mL and 1.7, respectively. This exceeded the IC50 in LNCaP, cells sensitive to androgens (9.1ug/mL). With increasing concentrations of SVT, the number of cells distributed in the S phase of cell cycle decreased significantly in comparison with cells from other phases.
To check whether SVT can inactivate NF-KB and induce apoptosis of cells to undergo PC-3 cells treated with SVT for 24 hours were evaluated. The SBR interacts with NF-KB signal molecules by a protein-protein interaction with the cysteine residues in the NF-KB molecules.
Cell culture SVT reduced the constitutive activation of NF-KB. Interaction between SSVTVT and mutant gene constructs was suggestive that the cysteine residues are the targets of SVT in the molecule NF-KB. The expression of proteins regulating cell cycle was also altered in the SVT treated cells with decreased expression of G2-M phase cyclin B1 protein regulation and regulatory proteins in G1 phase cells. Increased apoptosis was confirmed by induction of caspase-3 and -9 activations by SVT.
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