Inhibition of Class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines |
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| Institution: | 1. Ghent University Hospital, Department of Critical Care Medicine, C. Heymanslaan 10, 9000 Ghent, Belgium;2. University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands;3. Ghent University, Laboratory of Medical Biochemistry and Clinical Analysis, Ghent, Belgium;4. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia;5. School of Medicine, Griffith University, Southport, QLD, Australia;6. Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia;7. Ghent University, Department of Diagnostic Sciences, Ghent, Belgium;8. Ghent University Hospital, Department of Laboratory Medicine, Ghent, Belgium;9. Royal Brisbane and Women''s Hospital, Department of Intensive Care Medicine, Brisbane, QLD, Australia;10. CHU Nîmes, Department of Anesthesiology and Critical Care, Nîmes, France;11. Royal Brisbane and Women''s Hospital, Department of Pharmacy, Brisbane, QLD, Australia;1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;2. State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China;3. RSKT Biopharma Inc., Dalian 116023, China;4. Dalian Medical University, Dalian 116044, China;5. Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China |
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| Abstract: | Hepatoma cells have a below-normal content of polyunsaturated fatty acids; this reduces lipid peroxidation and the production of cytotoxic and cytostatic aldehydes within the cells. In proportion to the degree of deviation, hepatoma cells also show an increase in the activity of Class-3 aldehyde dehydrogenase, an enzyme important in the metabolism of lipid peroxidation products and also in that of several drugs. When hepatoma cells with different degrees of deviation were enriched with arachidonic acid and stimulated to peroxidize by ascorbate/iron sulphate, their growth rate was reduced in proportion to the quantity of aldehydes produced and to the activity of aldehyde dehydrogenase. Therefore, 7777 cells, less deviated and with low Class-3 aldehyde dehydrogenase activity, were more susceptible to lipid peroxidation products than JM2 cells. It is noteworthy that repeated treatments with prooxidant also caused a decrease in mRNA and activity of Class-3 aldehyde dehydrogenase, contributing to the decreased growth and viability. Thus, Class-3 aldehyde dehydrogenase could be considered relevant for the growth of hepatoma cells, since it defends them against cell growth inhibiting aldehydes derived from lipid peroxidation. |
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