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A Combination of Low Doses of Curcumin and Gramicidin Selectively kills Cancer Cells that Express Multidrug Resistance‐linked ABCG2 Transporter
Author(s) -
Rao Divya K,
Ambudkar Suresh V,
Mayer Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.966.4
Subject(s) - abcg2 , hek 293 cells , curcumin , transporter , atp binding cassette transporter , cancer cell , pharmacology , chemistry , multiple drug resistance , flow cytometry , biology , biochemistry , microbiology and biotechnology , cancer , receptor , gene , antibiotics , genetics
The ATP‐binding cassette (ABC) G2 (also called breast cancer resistance protein, BCRP) is a transporter that provides malignant cells with a mechanism to evade chemotherapy by developing multidrug resistance (MDR). This phenomenon has led to wide spread interest in developing strategies to circumvent ABC transporter‐mediated MDR in cancer cells. This study reports a strategy to selectively kill cancer cells that overexpress the ABCG2 transporter. The control vector‐transfected HEK 293 and HEK 293‐ABCG2 cells were treated with curcumin, the bioactive compound in turmeric, and gramicidin A (gA), a pore‐forming peptide from Bacillus brevis. The treatment of cells with sub‐toxic doses of curcumin, or gA had no effect on the viability of HEK‐control cells or HEK‐ABCG2 cells. However, the simultaneous administration of sub‐toxic doses of curcumin (2 μM) and gA (35 nM) selectively killed HEK‐ABCG2 cells and inhibited the transport function of ABCG2 as measured by flow cytometry, while HEK 293‐control cells remained unaffected. Consistent with previously published data, curcumin stimulated ATP hydrolysis by ABCG2, while gA did not have an effect on basal and curcumin‐stimulated ATPase activity of this transporter. These results suggest that gA enhances the cytotoxic effect of curcumin without interacting directly with the ABCG2 transporter. Taken together, these findings provide a potential strategy to target, in particular, those malignant cancer cells that develop MDR due to overexpression of ABCG2 transporter.