Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells

doi:10.1007/s00204-023-03456-w

Chia Nan University of Pharmacy & Science Institutional Repository > 行政單位 > 456 > Item 310902800/34911

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標題:	Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells
作者:	Yang, Hsin-Ling Lin, Ping-Yu Vadivalagan, Chithravel Lin, Yi-An Lin, Kai-Yuan Hseu, You-Cheng
貢獻者:	China Med Univ, Inst Nutr, Coll Hlth Care China Med Univ, Coll Pharm, Dept Cosmeceut Chi Mei Med Ctr, Dept Med Res Chia Nan Univ Pharm & Sci, Dept Biotechnol Asia Univ, Dept Hlth & Nutr Biotechnol China Med Univ, Chinese Med Res Ctr China Med Univ, Res Ctr Chinese Herbal Med
關鍵字:	CoQ(0) HIF-1 alpha NLRP3 inflammasome EMT Warburg effects
日期:	2023
上傳時間:	2024-12-25 11:05:31 (UTC+8)
出版者:	SPRINGER HEIDELBERG
摘要:	Coenzyme Q(0) (CoQ(0)) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ(0) (0-4 mu M) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg effects via HIF-1 alpha inhibition in triple-negative breast cancer (MDA-MB-231 and 468) cells. MTT assay, cell migration/invasion assays, Western blotting, immunofluorescence, metabolic reprogramming, and LC-ESI-MS were carried out to assess the therapy potential of CoQ(0). CoQ(0) inhibited HIF-1 alpha expression and suppressed the NLRP3 inflammasome and ASC/caspase-1 expression, followed by downregulation of IL-1 beta and IL-18 expression in MDA-MB-231 and 468 cells. CoQ(0) ameliorated cancer stem-like markers by decreasing CD44 and increasing CD24 expression. Notably, CoQ(0) modulated EMT by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal marker N-cadherin. CoQ(0) inhibited glucose uptake and lactate accumulation. CoQ(0) also inhibited HIF-1 alpha downstream genes involved in glycolysis, such as HK-2, LDH-A, PDK-1, and PKM-2 enzymes. CoQ(0) decreased extracellular acidification rate (ECAR), glycolysis, glycolytic capacity, and glycolytic reserve in MDA-MB-231 and 468 cells under normoxic and hypoxic (CoCl2) conditions. CoQ(0) inhibited the glycolytic intermediates lactate, FBP, and 2/3-PG, and PEP levels. CoQ(0) increased oxygen consumption rate (OCR), basal respiration, ATP production, maximal respiration, and spare capacity under normoxic and hypoxic (CoCl2) conditions. CoQ(0) increased TCA cycle metabolites, such as citrate, isocitrate, and succinate. CoQ0 inhibited aerobic glycolysis and enhanced mitochondrial oxidative phosphorylation in TNBC cells. Under hypoxic conditions, CoQ(0) also mitigated HIF-1 alpha, GLUT1, glycolytic-related (HK-2, LDH-A, and PFK-1), and metastasis-related (E-cadherin, N-cadherin, and MMP-9) protein or mRNA expression in MDA-MB-231 and/or 468 cells. Under LPS/ATP stimulation, CoQ(0) inhibited NLRP3 inflammasome/procaspase-1/IL-18 activation and NF kappa B/iNOS expression. CoQ(0) also hindered LPS/ATP-stimulated tumor migration and downregulated LPS/ATP-stimulated N-cadherin and MMP-2/-9 expression. The present study revealed that suppression of HIF-1 alpha expression caused by CoQ(0) may contribute to inhibition of NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects of triple-negative breast cancers.
關聯:	Archives of Toxicology, v.97, n.4, pp.1047-1068
显示于类别:	[行政單位] 456

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