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

Annu Arora1, Yogeshwer Shukla

  • 1Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, M.G. Marg, P.O. Box 80, Lucknow-226001, India.

Cancer Letters
|December 20, 2002
PubMed

Insights

Indole-3-carbinol (I3C) effectively reverses P-glycoprotein (P-gp) over-expression, a cause of cancer drug resistance. This finding suggests I3C

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • P-glycoprotein (P-gp) over-expression, encoded by the mdr-1 gene, is a key mechanism of multidrug resistance in cancer chemotherapy.
  • Vinca-alkaloids like vinblastine and vincristine are known to induce mdr-1 gene expression and P-gp over-expression.

Purpose of the Study:

  • To investigate the potential of indole-3-carbinol (I3C) to modulate P-gp over-expression induced by vinblastine or vincristine.
  • To evaluate I3C as a dietary adjuvant for reversing multidrug resistance in cancer treatment.

Main Methods:

  • Western blotting using a monoclonal antibody (clone JSB1) to detect P-gp levels.
  • Immunohistochemical staining of tissue sections followed by image analysis for P-gp quantification.

Main Results:

  • I3C significantly reversed the over-expression of P-gp induced by vinblastine and vincristine.
  • Image analysis confirmed that I3C effectively inhibited P-gp over-expression in vinca-alkaloid treated samples.

Conclusions:

  • Indole-3-carbinol (I3C) demonstrates significant potential in inhibiting P-gp over-expression.
  • I3C may serve as a valuable dietary adjuvant to overcome multidrug resistance in cancer therapy.

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