Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol.
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.
Arora
Annu
A
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, M.G. Marg, P.O. Box 80, Lucknow-226001, India.
Shukla
Yogeshwer
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019450:Genes, MDR; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014750:Vincristine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016588:Anticarcinogenic Agents; D002121:Calcium Channel Blockers; D007211:Indoles; D014750:Vincristine; D014747:Vinblastine; C016517:indole-3-carbinol; D014700:Verapamil