Affiliation:
1. Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India
2. Department of Chemistry, Pondicherry University, Puducherry 605014, India
Abstract
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine