3,3′-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants

Rahimi, Massod; Huang, Kai-Ling; Tang, Careen K.

doi:10.1016/j.canlet.2010.02.014

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Volume 295, Issue 1 , Pages 59-68, 1 September 2010

3,3′-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants

Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, United States

Received 6 January 2010; received in revised form 15 February 2010; accepted 16 February 2010. published online 18 March 2010.

Abstract

Epidermal Growth Factor Receptor (EGFR) mutants are associated with resistance to chemotherapy, radiation, and targeted therapies. Here we found that the phytochemical 3,3′-Diindolylmethane (DIM) can inhibit the growth and also the invasion of breast cancer, glioma, and non-small cell lung cancer cells regardless of which EGFR mutant is expressed and the drug-resistant phenotype. DIM reduced an array of growth factor signaling pathways and altered cell cycle regulators and apoptotic proteins favoring cell cycle arrest and apoptosis. Therefore, DIM may be used in treatment regimens to inhibit cancer cell growth and invasion, and potentially overcome EGFR mutant-associated drug resistance.

Keywords: EGFR, Mutants, Drug-resistance, Growth, Invasion, DIM