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Induction of intracellular acyl-CoA:cholesterol acyltransferase activity in glioblastoma cells by lidocaine
Authors:I Jeng  N Klemm  S Bressie  L Samson
Affiliation:1. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;2. Key Laboratory of Biological Nanotechnology of National Health Commission, Xiangya Hospital, Changsha 410008, China;1. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570200, China;2. Hainan Key Laboratory of Tropical Microbe Resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences & Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan Province, Hainan Institute for Tropical Agricultural Resources, Haikou 571101, China;3. School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou 510275, China;4. Laboratory Animal Center of Guangdong Medical University, Dongguan 523808, China;1. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;2. Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;3. Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;4. Shanghai Runshi Pharmaceutical Technology Co., Ltd., Shanghai 201218, China;5. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China;6. University of Chinese Academy of Sciences, Beijing 100049, China;7. Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
Abstract:The perturbation of cellular cholesteryl ester biosynthesis in glioblastoma C-6 cells by lidocaine was investigated. Lidocaine specifically inhibited the incorporation of radioactive oleic acid into cellular cholesteryl ester but had no significant effect on the incorporation of oleic acid into phosphatidylcholine. Oxygenated cholesterol-enhanced cholesteryl ester formation was less sensitive to lidocaine inhibition. Several other local anesthetics were compared. Lidocaine altered cholesteryl ester formation in time- and dose-dependent manners. Lidocaine was a powerful inhibitor initially and its potency declined with time. Lidocaine was capable of directly inhibiting acyl-CoA:cholesterol acyltransferase (ACAT) activity in broken cell homogenates. The lidocaine-mediated inhibition of cellular cholesteryl ester formation triggered an enhanced intracellular ACAT activity that was not fully expressed in the presence of lidocaine. The activation of ACAT activity by lidocaine might represent a compensatory mechanism by which the inhibitory effect of lidocaine was partially overcome with time.
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