Indole Curcumin Reverses Multidrug Resistance by Reducing the Expression of ABCB1 and COX2 in Induced Multidrug Resistant Human Lung Cancer Cells

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Author(s): Sankar Pajaniradje, Kumaravel Mohankumar, Rakesh Radhakrishnan, Shamim Akhtar Sufi, Srividya Subramanian, Parthiban Anaikutti, Surya Prakash Rao H, Rukkumani Rajagopalan*.

Journal Name: Letters in Drug Design & Discovery

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Drug resistance by the cancer cells towards current chemotherapeutic approaches poses a great challenge. In the present study, an Indole analogue of a well-known plant derived anticancer molecule, Curcumin, was tested for its multidrug resistance (MDR) reversing potential in induced multi drug resistant A549 cell line. Human lung cancer cell line A549 was made multidrug resistant (MDR) by prolonged treatment with low dosage of Docetaxel, an established anticancer drug. The MDR induction was confirmed by morphological evidence, Hoechst 33342 staining, MTT assay, Rhodamine123 and RT-PCR of ABCB1 gene. The induced MDR A549 cells exhibited significant increase in the gene expression of ABCB1 gene at transcriptional level. Retention and efflux studies with P-glycoprotein (P-gp) substrate Rh123 indicated that indole curcumin inhibited P-gp mediated efflux of Rhodamine. Furthermore, treatment of MDR A549 cells with indole curcumin showed down-regulation of gene expression of ABCB1 and COX2. This was also confirmed from the decreased protein level expression of COX2. In conclusion, the results of the present study indicate that indole curcumin reverses multi drug resistance by downregulating the expression of ABCB1 and COX2 genes. Thus, indole curcumin may act as a potent modulator for ABCB1 and COX2 mediated MDR in lung cancer.

Keywords: Multidrug resistance (MDR), MDR reversal, Curcumin, Indole curcumin, Docetaxel (Dtx), Lung cancer

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(E-pub Ahead of Print)
DOI: 10.2174/1570180817666200402124503
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