The effect of SAMe and betaine on Hepa 1-6, C34 and E47 liver cell survival in vitro.
In recent years, methyl one-carbon metabolism has received a great deal of attention because the disruption of methyl balance in a variety of genetically modified mice is associated with the development of various forms of liver injury, namely fatty liver disease and hepatocellular carcinoma (HCC). In addition, patients with liver disease often have an abnormal expression of key genes involved in methionine metabolism as well as elevated serum levels of methionine and homocysteine (Hcy). S-adenosylmethionine (SAMe) has rapidly moved from being a methyl donor to a key metabolite that regulates hepatocyte proliferation, necrosis and differentiation. Biosynthesis of SAMe occurs in all mammalian cells as the first step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase (MAT). Decreased hepatic SAMe biosynthesis is a consequence of numerous forms of chronic liver injury. In an animal model of chronic liver SAMe deficiency, the liver is predisposed to further injury and develops spontaneous steatohepatitis and HCC. SAMe treatment in experimental animal models of liver injury shows hepatoprotective properties. Meta-analyses also showed that it is effective in the treatment of patients with cholestatic liver diseases. We studied the survival of liver cells treated with SAMe and betaine using Hepa 1-6 and E47/C34 cell lines. We showed that exogenous SAMe decreased the number of Hepa 1-6 and E47/C34 cells, and increased the number of dead cells in vitro. Betaine had no significant effect on the number of surviving cells and the number of dead cells. The combination of both methyl donors significantly increased the survival of liver cells and reduced necrosis, compared to SAMe alone. This study showed the inhibition of the proliferation and increased necrosis in response to SAMe on liver cancer cell lines Hepa 1-6 and C34.
Department of Hematology, LA Biomed, Torrance, CA 90502, USA. joliva@labiomed.org
Joan
J
Oliva
Jin
J
Zhong
Virgil S
VS
Buslon
Samuel W
SW
French
D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013997:Time Factors
D001622:Betaine; D012436:S-Adenosylmethionine