Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL.

Hepatocellular carcinoma is a type of tumor highly resistant to available chemotherapeutic agents. The treatment of hepatocellular carcinoma remains a challenge that needs new approaches in the future. In a previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in human liver cancer cells (HepG2), and that combining CHCl(3)-F with green tea extracts (GTE) results in enhanced effects of anticancer activity in the cells. To further understand the mechanism of the anticancer activity of combining CHCl(3)-F and GTE in HepG2 cells, we investigated whether the addition of a mixture of CHCl(3)-F and GTE would affect the expression of APRIL (a proliferation-inducing ligand), which was expressed in HepG2 cells from 4 hours of incubation in vitro. We have shown that CHCl(3)-F and GTE enhanced anti-cancer activity by reducing the expression of APRIL. We speculate that the CHCl(3)-F and GTE mixture might provide a lead to a new drug design to treat hepatocellular carcinoma in the future.

Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells.

Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health. We therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27(Kip1) levels and the hypohosphorylation of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl(3)-F treatment alone.

Mechanism of growth inhibitory effect of Blumea balsamifera extract in hepatocellular carcinoma.

Blumea balsamifera is known to improve physiological disorders such as rheumatism and hypertension, but its anticancer activity has not been well elucidated. In this study, we found that Blumea balsamifera MeOH extract (BME) induced growth-inhibitory activity in rat and human hepatocellular carcinoma cells without cytotoxicity in rat hepatocytes which were used as a normal cell model. BME induced cell cycle arrest at the G1 phase via decreases in the expression of cyclin-E and phosphorylation of retinoblastoma protein. Furthermore, BME reduced the level of a proliferation-inducing ligand, that stimulates tumor cell growth. These findings suggest that BME has possible therapeutic potential in hepatoma cancer patients and that depletion of cellular APRIL is an important mechanism in the growth-inhibitory effect of BME.

Anticancer activities and mechanisms of Blumea balsamifera extract in hepatocellular carcinoma cells.

Blumea balsamifera (also known as sambong), a medicinal plant, is known to improve physiological disorders such as rheumatism and hypertension. However, its anticancer activity has not been well elucidated. In this study, we found that Blumea balsamifera MeOH extract (BME) induced growth inhibitory activity in rat and human hepatocellular carcinoma cells (McA-RH7777, HepG2, respectively) without cytotoxicity as in with rat hepatocytes used as a normal cell model. BME induced cell cycle arrest at G1 phase via decreases in expression of cyclin-E and phosphorylation of retinoblastoma (Rb) protein in both dose- and time-dependent manners. Furthermore, BME reduced the level of a proliferation related ligand (APRIL) which stimulates tumor cell growth. The anti-proliferative effect of BME was improved slightly but significantly by the treatment with recombinant human APRIL. These findings suggest that BME may have a possible therapeutic potential in hepatoma cancer patients and the depletion of cellular APRIL may be one of the important mechanisms on the growth inhibitory effect of BME.