Effect of curcumin on doxorubicin-induced cytotoxicity in H9c2 cardiomyoblast cells

ABSTRACT

Doxorubicin [DOX], a widely used chemotherapeutic agent can give rise to serve cardiotoxicity by inducing apoptosis. Curcumin, the active compound of the rhizome of Curcuma longa L. has anti-inflammatory, antioxidant and anti-proliferative activities. Curcumin has been identified to increase cytotoxicity in several cancer cell lines in combination with DOX, but there is no study about its effect and DOX on normal cardiac cells. Therefore, in the present study, we evaluated the effect of curcumin on apoptosis induced by DOX in H9c2 rat heart-derived cells. Cell viability was determined by MTT assay. Also, activation of caspase-3 was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the expression of c-IAP1. Detection of intracellular DOX accumulation was performed by flow cytometry. No toxicity observed when the cells exposed for 1 hr to different concentrations of curcumin, but pretreatment of cells with curcumin increased cytotoxicity of DOX in a dose dependent manner. Analysis of caspase-3 activation showed that curcumin pretreatment increased caspase-3 activation. RT-PCR analysis clearly showed that curcumin significantly decreased mRNA gene expression of c-IAP1 compared to cells treated with DOX alone. Pretreatment of H9c2 cells with DOX and curcumin had no effect on the intracellular accumulation of DOX. Our observations indicated that subtoxic concentrations of curcumin sensitize H9c2 cells to DOX-induce apoptosis. These results suggest that the use of curcumin in combination with DOX in malignancy must be reevaluated