Dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and Hep G2 hepatoma cells

AIM To investigate whether Dihydromyricetin(DHM) inhibits cell proliferation and promotes apoptosis by downregulating Notch1 expression.METHODS The correlation between Notch1 and Hes1(a Notch1 target molecule) expression in hepatoma samples was confirmed by q RT-PCR. In addition, MTT assays, flow cytometry and TUNEL analysis showed that DHM possessed strong anti-tumor properties, evidenced not only by reduced cell proliferation but also by enhanced apoptosis in QGY7701 and Hep G2 hepatocellular carcinoma(HCC) cells. The expressions of Notch1, Hes1, Bcl-2 and Bax were determined by Western blot.RESULTS Among the tested samples(n = 64), the expression levels of Notch1(75% of patients) and Hes1(79.7% of patients) m RNA in tumor tissues were higher than in the normal liver tissues. There was a negative correlation between the expression of Notch1 and the degree of differentiation and positively correlated with the Alpha Fetal Protein concentration. The viability of HCC cells treated with DHM was significantly inhibited in a dose and time-dependent manner. Apoptosis was induced in Hep G2 and QGY7701 cell lines following 24 h of DHM treatment. After treatment with DHM, the protein expression of Notch1 was downregulated, the apoptosis-related protein Bax was upregulated and Bcl2 was downregulated. Notch1 si RNA further enhanced the anti-tumor properties of DHM. CONCLUSION Notch1 is involved in the development of HCC and DHM inhibits cell proliferation and promotes apoptosis by down-regulating the expression of Notch1.

Therapeutic potential of stem cell in liver regeneration

Liver transplantation is the only life-saving procedure for patients with end-stage liver disease.However,its potential benefits are hampered by many disadvantages,such as the relative shortage of donors,operative risks,and high costs.These issues have prompted the search for new alternative therapies for irreversible liver disease.Stem cell therapy,with the ability for self-renewal and potential for multilineage differentiation,is a promising alternative approach.Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease.However,a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations;e.g.the lack of suitable cell sources and risk of teratoma formation.This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease,including the sources,mechanisms,and delivery methods of hepatic stem cells in liver regeneration,and discusses some challenges for their therapeutic application.