Dual effects of gossypol on human hepatocellular carcinoma via endoplasmic reticulum stress and autophagy. (August 2019)

• Record Type: Journal Article
• Authors: Zhang, Guang; Wang, Zhongxia; Chen, Weibo; Cao, Yin; Wu, Junyi; Qiang, Guanghui; Ji, Anlai; Wu, Junhua; Jiang, Chunping
• Is Part Of: International journal of biochemistry & cell biology. Volume 113(2019)
• Page Start: 48
• Page End: 57
• Publication Date: 2019-08
• Subjects: HCC hepatocellular carcinoma -- ER endoplasmic reticulum -- UPR unfolded protein response -- IRE-1α inositol-requiring enzyme 1 alpha -- CHOP C/EBP homologous protein -- CQ chloroquine -- eIF2α eukaryotic initiation factor 2α -- CCK-8 cell counting kit-8 -- OD optical density -- PI propidium iodide -- TEM Transmission electron microscopy -- IHC immunohistochemistry -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling -- PARP poly ADP ribose polymerase -- NC negative control -- BiP binding immunoglobulin protein; Hepatocellular carcinoma -- Gossypol -- Apoptosis -- Endoplasmic reticulum stress -- Autophagy; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2019.05.012
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Treatment outcomes for hepatocellular carcinoma (HCC) remain unsatisfactory, and effective new therapeutic methods are urgently needed. Gossypol has been shown to have an anti-HCC effect, but the underlying mechanism requires further study. In this study, we found gossypol inhibited HCC cells in vitro and in vivo. Typical apoptosis was induced in HCC cells. Dilated ER and autophagosomes were observed by electron microscopy, and the activation of the unfolded protein response and autophagy markers suggested that gossypol induced both ER stress and autophagy. C/EBP homologous protein was the key factor that led to apoptotic cell death, whereas inositol-requiring enzyme 1α and eukaryotic initiation factor 2α played a protective role. Autophagy protected the cells from ER stress-related apoptosis. Both in vitro and in vivo studies indicated that inhibition of autophagy enhanced the anti-HCC effect of gossypol. Taken together, ER stress is the molecular mechanism underlying gossypol-induced apoptosis and autophagy. Gossypol exhibits anti-HCC activity primarily through the activation of apoptosis. However, gossypol-induced autophagy protects HCC cells from ER stress. Therefore, a combination therapy of gossypol and autophagy inhibitors may lead to an enhanced anti−HCC effect.