B19, a Novel Monocarbonyl Analogue of Curcumin, Induces Human Ovarian Cancer Cell Apoptosis via Activation of Endoplasmic Reticulum Stress and the Autophagy Signaling Pathway

Abstract

Background: The unfolded protein response, autophagy and endoplasmic reticulum (ER) stress-induced apoptosis regulate tumor cell fate and have become novel signaling targets for the development of cancer therapeutic drugs. Curcumin has been used to treat several different cancers, including ovarian cancer, in clinical trials and research; however, the role of ER stress and autophagy in the therapeutic effects of curcumin and new curcumin analogues remains unclear.Methods: Cell viability was determined using the MTT assay. Apoptosis was detected using flow cytometry with PI/Annexin V-FITC staining. The expression levels of ER stress- and autophagy-related proteins were analyzed by western blotting. The activation of autophagy was detected using immunofluorescence staining.Results: We demonstrated that B19 induced HO8910 cell apoptosis in a dose-responsive manner. We also determined and that this effect was associated with corresponding increases in a series of key components in the UPR and ER stress-mediated apoptosis pathways, followed by caspase 3 cleavage and activation. We also observed that B19 treatment induced autophagy in HO8910 cells. The inhibition of autophagy using 3-methyladenine (3-MA) increased levels of intracellular misfolded proteins, which enhanced ovarian cancer apoptosis.Conclusions: Our data indicate that ER stress and autophagy may play a role in the apoptosis that is induced by the curcumin analogue B19 in an epithelial ovarian cancer cell line and that autophagy inhibition can increase curcumin analogue-induced apoptosis by inducing severe ER stress.

Identification of compound CA-5f as a novel late-stage autophagy inhibitor with potent anti-tumor effect against non-small cell lung cancer

“…Curcumin is a natural polyphenol derived from the herb Curcuma longa that suppresses the growth of various types of cancer cells by regulating autophagy [20][21][22][23]. Although poor bioavailability in vivo limits its clinical applications, curcumin remains a good lead compound for further structure modification, as an increasing number of curcumin analogs or derivatives have been reported to induce autophagy and kill cancer cells [24][25][26]. Several studies have demonstrated that curcumin is capable of inducing autophagy in different lines of human tumor and normal cells [22,23,[27][28][29].…”

Saururus chinensis Baill induces apoptosis through endoplasmic reticulum stress in HepG2 hepatocellular carcinoma cells

“…3A and B). The activation of IRE1a, PERK and ATF6 has been reported to increase CHOP protein expression, activating and initiating the ER stressinduced apoptotic cascade (Qu et al, 2013;Chen et al, 2014;Liu et al, 2014;Yang et al, 2014). We observed that the protein expression levels of IRE1a and CHOP were increased after treatment with SC-E in HepG2 cells.…”

Curcumin Analogue CA15 Exhibits Anticancer Effects on HEp-2 Cells via Targeting NF-κB

“…As a curcumin analogue with greater bioavailability and biological activity, EF24 is able to inhibit proliferation of colon cancer cells and migratory of melanoma cells [27, 28]. Another curcumin analogue, B19, is also found to exert antiangiogenic activity and induce apoptosis of ovarian cancer cells [29, 30]. However, their toxicities towards normal cells are always neglected.…”