Chemosensitizing effect of Curcumin with Arsenic Trioxide on Normal and Cancerous Liver Cell Line

Abstract

Arsenic (Arsenic trioxide) and turmeric (Curcumin) separately are the traditional remedy for newlinedifferent diseases since ages. Nowadays, Arsenic trioxide alone is an FDA approved drug used newlineclinically for the treatment of acute promyelocytic leukemia (APL) by targeting PML/RARA newlinewhile curcumin shows anti-tumor properties in different cancers. Curcumin has antiviral activities newlineand affected binding and fusion of HCV virus by changing fluidity of virus envelope that further newlineinhibits the entry of HCV genotypes. Also, conjugated curcumin with albumin shows tumor newlineinhibition, anticancer and immunomodulatory properties by inducing G2/M phase cell cycle newlinearrest and induces apoptosis in several hepatoma cell lines. However, curcumin is known to newlineattenuate liver disease through the modulated lipid metabolism, release of inflammation newlinecytokines, decreases oxidative stress and enhances the sensitivity of insulin. In the present study, newlinewe assessed the effects of arsenic trioxide and curcumin alone and in combination on cell newlineviability, cell cytotoxicity, colony formation, induction of apoptosis, different apoptotic related newlinegene or protein expression, changes in ROS, membrane potential and lipid peroxidation and cell newlinemotility in liver normal and cancer cells. In our studies, we used multiple assays such as MTT newlineassay, WST assay, Trypan blue assay, Colony formation assay, FACS and spectroscopy assay, Q- newlinePCR, western blotting, ROS assay, Membrane potential analysis, lipid peroxidation analysis and newlinecell motility assay to check the overall effect of arsenic trioxide and curcumin combination on newlinecell survival, tumor growth and cell apoptosis in normal and cancerous liver cells. newlineThe cell viability decreases and cell cytotoxicity increases in arsenic trioxide and curcumin newlinecombination treated cells in both cell line in dose-dependent manner, which was consistent with newlineinduction of apoptosis, perhaps cancer cells is most affected as compare to normal cells. The gene newlineand protein expression of cell survival and apoptotic related proteins also gives the