title: Regulation of HA14-1 mediated oxidative stress, toxic response, and autophagy by curcumin to enhance apoptotic activity in human embryonic kidney cells.
abstract: An alteration in susceptibility to apoptosis not only contributes to promotion of malignancy but can also enhance drug resistance in response to anticancer therapies. HA14-1 is a small molecule which has the potential of inducing apoptosis in cancerous cells. HA14-1 manifests an antagonistic effect on antiapoptotic protein Bcl-2 and consequently induces cell death in various cancerous cell lines. However, it is also known to generate ROS and toxic response in the cells upon decomposition. Elevated level of ROS is responsible for oxidative stress and other pathological consequences, if not metabolized properly. The aim of the present study was to examine the synergistic effect of curcumin in promoting apoptosis by regulating the HA14-1 mediated ROS generation, toxicity, oxidative stress, and autophagy in human embryonic kidney cells. Our study demonstrates that curcumin efficiently scavenges HA14-1 mediated generation of ROS and toxic response resulting in augmentation of apoptosis in HEK 293T cells by promoting inhibition of antiapoptotic proteins and process of autophagy. Thus curcumin along with HA14-1 regulates cell proliferation by disruption of the antiapoptotic signaling mechanism. This approach could serve as a promising strategy for therapeutic potential to overcome their adverse effects.
authors.affiliation: Cell Biology Department, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Koba, Gandhinagar, Gujarat, India.
authors.forename: Kishu
authors.initials: K
authors.lastname: Ranjan
authors.forename: Anupama
authors.initials: A
authors.lastname: Sharma
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Chandramani
authors.initials: C
authors.lastname: Pathak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D003474:Curcumin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C498143:RELA protein, human; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D002374:Catalase; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin
keywords: HA14-1; ROS; apoptosis; autophagy; curcumin; cytotoxicity; oxidative stress