# D336 The regulation of transcription factors STAT-3 and NF-ęB for inhibition of VEGF by S-adenosylmethionine in human hepatoma cell line HepG2. Weihua Qiu, Bingsen Zhou, Donald David, Shenxian Qian, Dana Darwish, Lijun Xue and Yun Yen, City of Hope National Medical Center, Duarte, CA. Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world causing many deaths annually. Despite recent advances in diagnostic and therapeutic management, prognosis of HCC still remains poor. S-adenosylmethionine (SAMe) is a methyl donor for biological transmethylation reactions in cells. SAMe is also a precursor of polyamine and participates in the synthesis of glutathione, the main cellular anti-oxidant in the liver. There is accumulating evidence that suggests the protective potential of SAMe in preserving liver function, such as two benefits of SAMe administration including attenuating experimental liver damage and improving survival of alcoholic patients with cirrhosis. Vascular endothelial growth factor (VEGF) has been verified to be closely related to the development and metastases of HCC. In this study, we demonstrated that the expression of VEGF in p53-wild type human hepatoma cell line HepG2 decreased significantly after SAMe treatment, whereas not much change occurred in normal embryonic liver cell line CL-48. Contrary to HepG2, p53-null human hepatoma cell line Hep3B revealed a stable expression of VEGF after SAMe administration. These results were confirmed by Northern blot and Western blot in a dose dependent manner. To better understand the mechanism of VEGF down-regulation after SAMe treatment, we examined the upstream regulation of signal transcription factors by Western blot. The results demonstrated that the Signal Transducers and Activators of Transcription -3 (STAT-3) played an important role in SAMe mediated VEGF down-regulation in HepG2 clone. Since STAT-3 has been reported as signal transducer of NF-ęB, further investigation focused on the role of NF-ęB in SAMe treatment using gel-shift and super shift system. Our results showed that nuclear extracts from HepG2 cells demonstrated specific interaction with NF-ęB, which could be super-shifted by anti NF-ęB antibody, and this interaction could be induced under the SAMe treatment. Thus, our study suggests the transcription regulation by STAT-3 and NF-ęB may be considered as a novel mechanism in SAMe-mediated hepatoprevention. Down-regulation of VEGF after SAMe treatment makes it possible for SAMe to be used as chemoprevention agent in HCC. (This study was sponsored by Parsons Foundation.) Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.