NATURAL POLYPHENOL BASED CARDIO-ONCOLOGICAL THERAPEUTICS IN DRUG INDUCED CARDIOTOXICITY
Author: Vibha Rani
Publisher:
Published: 2017
Total Pages:
ISBN-13:
DOWNLOAD EBOOKBackground: Cardiotoxicity of anti-cancer drugs has emerged as an important factor for cardiovascular complications. There is a growing interest in natural bioactive compounds for targeting the same. Objectives: Synergystic cardio-protective effects of Curcumin were studied in Doxorubicin (Dox) mediated cardiotoxicity. Methodology: Curcumin mediated effects were investigated by various in vitro, in silico and in vivo studies. Various concentration and time dependent cell viability assays were conducted for Dox and Curcumin followed by microscopic, molecular and biochemical assays. In silico docking studies of Curcumin and Dox with cardiac stress molecules were performed. The findings were validated in vivo at transcriptomic and proteomic levels by expression studies. Synergistic effect was also studied on human breast cancer cell line by various assays. Results: We observed that Dox induced cardiotoxicity occurs through ROS over production by exaggerating the inbuilt antioxidants. Interestingly, our study proposes that Curcumin exerts time-dependent opposite responses and validated by docking. Curcumin supplementation in cancer cells exaggerates oxidative stress and results in tumor by modulating pro- and anti-apoptotic biomarkers. In silico docking studies also proposed the signalling pathways operative in curcumin responses. Conclusions: Pre-treatment of Curcumin can suppress the Dox induced cardiotoxicity and supplementing curcumin results in achieving the desired anti-cancerous effect of Dox without compromising its activity thereby reducing dose mediated Dox effects. Hence, Curcumin holds a great potential as future cardio-oncological therapeutics.