Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol.

Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, M.G. Marg, P.O. Box 80, Lucknow-226001, India.

Cancer letters 2003 Jan 28

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The over-expression of mdr-1 gene transcript P-glycoprotein (P-gp), responsible for multiple drug resistance, is one of the major obstacles in cancer chemotherapy. In the present study, indole-3-carbinol (I3C), a well-known chemopreventive agent present in cruciferous vegetables, has been evaluated for its potential to modulate the over-expression of P-gp induced by vinblastine or vincristine, which are known inducers of mdr-1 gene. The results revealed that I3C significantly reversed the over-expression of P-gp in vinca-alkaloid induced drug resistance as evident by Western blotting using monoclonal antibody (clone JSB1). Quantization of immunostained tissue sections using image analysis technique revealed that vinblastine/ vincristine induced overexpression of P-gp was effectively reversed by I3C. The present investigation suggests that I3C can significantly inhibit the P-gp over-expression and may have utility as a dietary adjuvant in the treatment of cancer for the reversal of multiple drug resistance.

Citation

Annu Arora, Yogeshwer Shukla. Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol. Cancer letters. 2003 Jan 28;189(2):167-73