Curcumin Downregulates Phosphate Carrier and Protects against Doxorubicin Induced Cardiomyocyte Apoptosis.

Lu Junkun,K C Sudeep,Hasahya Tony,Li Xin,Zhang Mingliang,Qi Xiangqian,Wang Yanqin,Chu Erfu

doi:10.1155/2016/1980763

Abstract

Aim. To explore the effects of curcumin on phosphate carrier (PiC) and its role in protection against doxorubicin induced myocyte toxicity. Methods. Using H9c2 cell line, the cardiotoxic effect of doxorubicin and its mitigation by curcumin were studied. H9c2 cells were cultured with doxorubicin and/or curcumin at various concentrations. Analysis for apoptosis of H9c2 was done using flow cytometry. Confocal laser scanning microscopy was used to record the fluorescence intensity ratios and to determine the mitochondrial permeability transition pore (MPTP) opening state. Oxidative stress was measured using glutathione level, superoxide dismutase activities, and malondialdehyde content. The effect of doxorubicin and curcumin on PiC gene expression was measured by real-time PCR. Results. Curcumin decreased mRNA of PiC and was partly protective against oxidative stress, loss of mitochondrial transmembrane potential, and apoptosis induced by doxorubicin. Interestingly, the effect was not clearly dose dependent and the concentration of 12 mg/L was more efficient than 15 and 10 mg/L. Conclusion. Curcumin downregulates PiC and partly protects against doxorubicin induced oxidative stress and myocyte apoptosis.

Highlights

Doxorubicin is a well-established and highly effective antineoplastic agent used to treat a broad range of cancers
The cardiotoxic effects of doxorubicin are thought to be mediated in part via disruption of mitochondrial function, increased opening of the mitochondrial permeability transition pore (MPTP), and cytochrome c release, with resulting myocyte apoptosis [4,5,6]
Given that that doxorubicin induced myocyte apoptosis is in part mediated via the MPTP, we investigated whether doxorubicin upregulates PiC and whether this is correlated to cellular apoptosis

Summary

Introduction

Doxorubicin is a well-established and highly effective antineoplastic agent used to treat a broad range of cancers. The cardiotoxic effects of doxorubicin are thought to be mediated in part via disruption of mitochondrial function, increased opening of the mitochondrial permeability transition pore (MPTP), and cytochrome c release, with resulting myocyte apoptosis [4,5,6]. It is hypothesized to have a role in cell death as either a component or a regulator of the mitochondrial permeability transition pore (MPTP) complex. Given that that doxorubicin induced myocyte apoptosis is in part mediated via the MPTP, we investigated whether doxorubicin upregulates PiC and whether this is correlated to cellular apoptosis. We examined the effect of curcumin, on PiC expression, and its protective role against doxorubicin induced myocyte apoptosis [9,10,11]

Methods

Results

Conclusion