Science

SAMe prevents formation of hepatocellular carcinoma in rats

Last Updated: 2009-08-05 15:45:16 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In a rat study of hepatocellular carcinoma (HCC), administration of S-adenosylmethionine (SAMe) reduced establishment and growth of new tumors. It was not effective at treating established HCC, however.

SAMe is synthesized by all mammalian cells and widely available as a nutritional supplement used - but not FDA-approved -- to treat depression and chronic pain, the research team points out.

In a prepared statement, lead researcher Dr. Shelly C. Lu from the University of Southern California in Los Angeles commented, "The observation that SAMe failed to exert any therapeutic effect in already established HCC is disappointing....Nevertheless, effectiveness of SAMe in chemoprevention of human HCC deserves study now."

As Dr. Lu and colleagues note in the August issue of Hepatology, it's known that chronic liver disease impairs hepatic SAMe biosynthesis and that mice with SAMe deficiency develop HCC. Furthermore, SAMe is anti-apoptotic in normal hepatocytes and selectively pro-apoptotic in human liver cancer cells.

Their present findings stem from experiments in rats that ordinarily develop 1-cm tumors within 2 weeks after injection of H4IIE hepatoma cells into the liver parenchyma.

When the rats were treated with SAMe by continuous infusion over 11 days, starting 24 hours after injection of the hepatoma cells, they had sharp and sustained increases in plasma and liver SAMe levels, according to the researchers, with hepatic levels increasing more than 10-fold.

"This regimen...was able to reduce tumor establishment and growth" as documented on MRI and visual inspection, the authors report.

"However," they continue, "if intravenous SAMe was started after HCC had already developed, it was ineffective in reducing tumor growth," with plasma SAMe levels rising but hepatic levels only "minimally increased."

With established tumors, SAMe administration led to "a compensatory induction in hepatic methyltransferase expression, which prevents SAMe accumulation to a level necessary for it to exert a pro-apoptotic effect on liver cancer cells."

The researchers speculate that along with its proapoptotic effects, SAMe might also limit tumor establishment by inhibiting angiogenesis.

Indeed, they found that SAMe "significantly induced the expression of type XVIII collagen, which is the precursor for an important antiangiogenic peptide, endostatin."

"SAMe has a short half-life so that either frequent dosing or continuous intravenous infusion will be necessary to maintain a high hepatic SAMe level," Dr. Lu and her associates conclude.

Hepatology 2009;50:462-471.