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.

Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro‐inflammatory cytokines in human breast adenocarcinoma cells

“…However, in the presence of NAC, the generation of intracellular ROS was down‐regulated, and cell death was revoked. Further, we discriminated the necrotic cell death by examining the release of LDH which releases upon plasma membrane damage . We found that PMsCur and Pluronic F127 were not showing necrotic cell death.…”

Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes

“…For example, cadmium (Cd) has been shown to induce autophagy in skin epidermal cells (Son et al 2011) and in vascular endothelial cells (Dong et al 2009), while inorganic mercury (Hg) has been shown to induce autophagic cell death in rat hepatocytes and glioma cells (Chatterjee et al 2012). In addition, oxidative stress-induced autophagy has been shown to be involved in apoptosis in vivo (Duan et al 2013) and in vitro (Ranjan et al 2014). However, autophagic cell death appears to be independent of apoptosis in transformed cancer cells (Chen and Gibson 2008).…”

Expression of cFLIPL Determines the Basal Interaction of Bcl‐2 With Beclin‐1 and Regulates p53 Dependent Ubiquitination of Beclin‐1 During Autophagic Stress

“…Establishment of GFP-LC3 stable cell lines. The pEGFP-LC3 expressing stable cell lines of HEK 293T cells were prepared as described earlier [Ranjan et al, 2014]. The GFP-LC3 expressing stable cells of HEK 293T were treated as described in the figure legends.…”