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Background: 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. Materials and Methods: 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 staining and RT-PCR of ABCB1 gene. Protein expression studies were carried out using western blotting technique Results and Discussions: The induced MDR A549 cells exhibited significant increase in the gene expression of ABCB1 gene at the transcriptional level. Retention and efflux studies with Pglycoprotein (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 downregulation of gene expression of ABCB1 and COX 2. This was also confirmed from the decreased protein expression of COX 2. Conclusion: The results of the present study indicate that indole curcumin reverses multi drug resistance by downregulating the expression of ABCB1 and COX 2 genes. Thus, indole curcumin may act as a potent modulator for ABCB1 and COX 2 mediated MDR in lung cancer.