Role of plant derived epigenetic inhibitor and its nanoparticle formulation in cancer therapy An involvement of apoptotic signalling pathway modulation

Abstract

newlineCancer poses a major health issue of mankind to date. According to the survey conducted by newlineGLOBOCAN, there were 17.0 million new cancer cases and 9.5 million deaths in 2018 newlineworldwide. Conventional treatment approaches of cancer have several limitations like newlineundesired toxicity, cancer resistance and recurrence of the disease. Epigenetic alteration newlinefollowed by permanent mutation of genes involved in cell growth and apoptosis is the newlinecommon hallmark of cancer. As the epigenetic changes are repairable, targeting the epigenetic newlinemechanism is a novel strategy in cancer therapy. Thus, researchers are in quest of plantderived newlineepigenetic inhibitors which are safe to the human body and may induce apoptosis of newlinecancer cells. Furthermore, biodegradable nanoparticles (NPs) have a prominent role in the newlinetargeted delivery of the bioactive molecules at the tumour site and their enhanced anticancer newlineefficacy. newlineThe present study was initiated with the investigation of in vitro anticancer activity of two newlinebioflavonoids silibinin (SBN) and quercetin (QCT) by evaluating cell viability, colony newlineformation efficiency and apoptosis of human lung and breast cancer cell lines A549 and newlineMDA-MB-468 respectively. The curative and preventive anticancer efficacy of SBN and QCT newlinewas carried out in cancer cell lines induced tumour xenograft model in C57BL6 mice. The role newlineof SBN and QCT in triggering cellular apoptotic signalling pathway through modulating newlinetumour suppressor gene (TSG) p53, proto-oncogene Bcl2 and superoxide dismutase (SOD) newlineenzyme activity was explored. Preclinical oral toxicity study showed that the test compounds newlinewere safe to the C57BL6 mice. newlineA novel formulation of QCT viz. QCT loaded chitosan nanoparticles (QCT-CS NPs) was newlineprepared by ionic gelation method. The NPs were successfully characterized for size, newlinepolydispersity index (PDI), zeta potential, drug-polymer compatibility and stability. The newlineformulation was tested for its in vitro and in vivo anticancer activity and exhibited improved newlineefficacy as compared to free QCT. In a