Augmented cytotoxic effects of paclitaxel by curcumin induced overexpression of folate receptor-α for enhanced targeted drug delivery in HeLa cells

Abstract

BackgroundNew targeted therapies are intended to minimize the toxic effects and maximize destruction of tumor cells. Folate is a membrane-bound receptor that plays a vital role in the uptake of anti-folate molecules aimed for efficient drug delivery of anti-folate drugs. PurposeThe present study is aimed at the modulation of the expression of folate receptor by curcumin that enhances the intake, cytotoxicity and anticancer effects of paclitaxel in HeLa cells. Materials and methodsHeLa cells were pretreated with curcumin and treated with paclitaxel. We measured the cell viability, uptake of radiolabelled folic acid and paclitaxel, Folate receptor –alpha (FR-α) protein expression by immunocytochemistry and western blot and FR-α mRNA expression by qualitative and quantitative analysis. ResultsThis study shows that curcumin (10 - 50 µM) causes significantly increased cytotoxicity in a dose and time dependent manner. It also enhances the intake of radiolabeled folic acid and paclitaxel 3–4 folds in HeLa cells. The pretreatment of HeLa cells with curcumin shows statistically significant of cell death by paclitaxel. The quantitative RT-PCR demonstrates the expression of FR- α mRNA upon curcumin treatment. Furthermore, immunochemistry and western blotting analysis proved that curcumin enhances expression the FR- α in HeLa cells. ConclusionOur study proved that the molecular mechanism of curcumin enhances the upregulation of FR – α mRNA and protein expression in HeLa cells. Therefore, a combination of curcumin and paclitaxel at less concentration may be a targeting strategy for FR-targeted drug delivery providing a better therapeutic intervention of cancer.