The anti-tumor activities of coenzyme Q0 through ROS-mediated autophagic cell death in human triple-negative breast cells. (March 2023)

• Record Type: Journal Article
• Authors: Yang, Hsin-Ling; Huang, Sheng-Teng; Lyu, Zi-He; Bhat, Asif Ali; Vadivalagan, Chithravel; Yeh, Yu-Lyu; Hseu, You-Cheng
• Is Part Of: Journal of functional foods. Volume 102(2023)
• Publication Date: 2023-03
• Subjects: CoQ0 -- TNBC -- Apoptosis -- Autophagy -- ROS; CoQ0 Coenzyme Q0 (2, 3-dimethoxy-5-methyl-1, 4-benzoquinone) -- EMT Epithelial-mesenchymal transition -- MTT 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- AO Acridine orange -- AVOs Acidic vesicular-organelles -- Z-VAD-FMK Z-Val-Ala-Asp-fluoro-methyl ketone -- 3-MA 3-Methyladenine -- CQ Chloroquine -- DCFH2-DA 2′, 7′-dihydrofluorescein-dictate -- ROS Reactive oxygen species -- NAC N-acetylcysteine; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2023.105454
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Coenzyme Q0 (CoQ0) inhibits proliferation and colony formation in MDA-MB-468 and 231 cells. CoQ0 induced apoptosis associated with caspase-3 activation and PARP cleavage. CoQ0 induced autophagic cell death is accompanied by LC3-II accumulation and AVO formation. Apoptosis inhibition suppresses CoQ0 -induced autophagy and autophagy inhibition suppresses CoQ0 -induced apoptosis. Antioxidant NAC prevents CoQ0-induced apoptosis and autophagy. Abstract: Coenzyme Q0 (CoQ0 ) obtained from Antrodia camphorata has therapeutic benefits in cancer treatment. Our previous findings in vivo and in vitro have shown that CoQ0 affects triple-negative breast cancer cells (TNBCs) by blocking EMT and metastasis. The current study investigated the cancer-preventive activities of CoQ0 on TNBC MDA-MB-468 and 231 cells by activating apoptotic and autophagic cell death. The CoQ0 treatment reduced colony development and proliferation in TNBC cells. In addition, CoQ0 triggered death activation by caspase-3 stimulation, PARP cleavage, and significantly affected Bax/Bcl-2 regulation. Autophagy was triggered by CoQ0, as shown by LC3-II accumulation, p62/SQSTM1 expression, ATG5 expression, ATG4B inhibition, AVO formation, and impeded Beclin-1/Bcl-2 regulation. In addition, transmission electron microscopy data showed that CoQ0 increased autophagosome formation. The antioxidant N -acetylcysteine substantially suppressed CoQ0 -mediated ROS generation and attenuated apoptotic- and autophagic-cell death by CoQ0 in TNBC cells. CoQ0 is a potential anticancer agent in treating human triple-negative breast cancers.