Effect of Curcuminoids on MDR Phenotype in Human Embryonic Kidney Cell Lines
Abstract
Background: Resistance to chemotherapy chemicals is a major obstacle to sucessful treatment of cancer. Out of the mechanism of drug resistance is characterized by the overexpression of drug transporters on plasma membrane such as P-glycoprotein (Pgp), multidrug resistance associated protein (MRP), especially MRP1. Curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were reportedly used to reverse multidrug resistance phenotype and increase chemotherapeutic sensitivity in cancer cells.
Aim: To investigate the effect of three curcuminoids on cell cytotoxicity and MDR phenotype in HEK293pcDNA3.1MRP1 cell line (drug resistance cell line) and HEK293pcDNA3.1 cell line (parental drug sensitive cell line).
Methods: Curcuminoids were examined for the effect on MDR phenotypes of the cells by cytotoxicity assay with MTT method. Treatments of cell lines with non-toxic dose (10 mM) of curcuminoids in combination with varying doses of etoposide VP16 (0-200 mM) for 72 hr were analysed.
Results: Curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibited cytotoxic activity on HEK293pcDNA3.1 MRP1 cell line with IC50 of 62.5, 68.7, and 56.3 mM, respectively. HEK293pc DNA3.1 showed IC50 of 53.1, 56.2, and 50 mM, respectively. At non-toxic dose of bisdemethoxycurcumin exhibited the highest effect on MDR phenotype, followed by curcumin and demethoxycurcumin, respectively.
Conclusion: Bisdemethoxycurcumin was an excellent MDR phenotype reversing which increased drug sensitivity in drug resistance cell line (HEK293pcDNA3.1MRP1 cell line). This finding shows the possibility of using curcuminoids as an MDR modulator in cancer patients however further experiments needs to be studied to achieve this goal.
