6-Shogaol mediated ROS production and apoptosis via endoplasmic reticulum and mitochondrial pathways in human endometrial carcinoma Ishikawa cells. (November 2020)

• Record Type: Journal Article
• Authors: Ma, Run-Hui; Ni, Zhi-Jing; Zhang, Fan; Zhang, Yuan-Yuan; Liu, Miao-Miao; Thakur, Kiran; Zhang, Jian-Guo; Wang, Shaoyun; Wei, Zhao-Jun
• Is Part Of: Journal of functional foods. Volume 74(2020)
• Publication Date: 2020-11
• Subjects: 6-shogaol -- Ishikawa cell -- ROS -- ER stress -- Mitochondria pathways; EC Endometrial cancer -- ROS reactive oxygen system -- CICAMS Cancer Hospital Chinese Academy of Medical Sciences -- WCRF World Cancer Research Fund -- GSH glutathione -- NAC N-Acetylcysteine -- HPLC-UV high-performance liquid chromatography - ultraviolet absorption detector -- LC-MS/MS Liquid chromatography-tandem mass spectrometry -- 5-FU 5-fluorouracil -- H&E hematoxylin and eosin staining -- MPF Mature Promoting Factor -- PS Phosphatidylserine -- Δψm mitochondrial membrane potential -- Fis1 fission 1 protein -- Drp1 dynamin-related protein 1 -- Mfn1 mitofusin 1 -- Mfn2 mitofusin 2 -- OPA1 optic atrophy1 -- ERO-1 endoplasmic reticulum oxidoreductin-1 -- FAD flavin adenine dinucleotide -- PDI UPR, unfolded protein response -- RIDD IRE1α‐dependent decay -- ERAD ER‐associated degradation -- ERpQC ER stress-induced pre-emptive quality control -- ER-phagy Degradation of accumulated proteins by autophagy -- S1P site-1 protease -- S2P site-2 protease -- ASK1 apoptosis signal-regulating kinase 1 -- TRAF2 tumor necrosis factor receptor associated factor 2 -- JNK c-Jun amino terminal kinase -- IP3R inositol triphosphate receptor -- MAM mitochondria-associated membranes -- MFN2 mitofusin‐2 -- BI-1 Bax-inhibitor-1 -- Apaf-1 activating factor-1; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2020.104178
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: 6-shogaol induced ROS generation in vitro and in vivo resulting in human endometrial cancer inhibition. 6-shogaol cleared intracellular glutathione as the potential mechanism against Ishikawa cell. Endoplasmic reticulum response biomarkers activated by 6-shogaol were associated with mitochondria mediated cell apoptosis. 6-shogaol targeting endoplasmic reticulum stress markers offers an innovative strategy to control endometrial cancer. Abstract: Endometrial cancer (EC) associated with endogenous hormone metabolism, obesity, diabetes, and inappropriate dietary habits has shown a rising trend in recent years. Various therapeutics methods including dietary approaches (vital phytochemicals) offer healthy and nontoxic strategies against cancer. To date, 6-shogaol as one of the antitumor phytochemicals remains unexplored against human endometrial cancer cells. In our study, 6-shogaol obtained from Zingiber officinale rhizomes separated and purified by HPLC, LC-MS/MS, and NMR respectively could inhibit Ishikawa cell proliferation at IC50 (24.91 μM) with the arrested cell cycle in the G2/M phase. Moreover, it promoted apoptosis, as a result, triggered ROS production, then activated key ER response biomarkers in Ishikawa cell associated with mitochondria, and ultimately regulated related genes and proteins in vitro and in vivo. Therefore, 6-shogaol can be used as a promising natural compound endowed with potential benefits for cancer treatment and/or prevention at large and EC in particular.