title: Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.
abstract: Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: zhangxd@nankai.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001391:Azo Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D066292:Lipid Droplets / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013859:Thiocarbamates / Q000494:pharmacology; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001391:Azo Compounds; D016328:NF-kappa B; D012333:RNA, Messenger; D013859:Thiocarbamates; D014280:Triglycerides; C066229:prolinedithiocarbamate; D002784:Cholesterol; D011392:Proline; D003066:Coenzyme A Ligases; C583414:ACSL1 protein, human; C011049:oil red O; D001241:Aspirin
keywords: ACSL1; Abnormal lipid metabolism; Aspirin; Hepatocellular carcinoma