Inhibition of esophageal-carcinoma cell proliferation by genistein via suppression of JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways.

Esophageal carcinoma (EsC) is a clinically challenging neoplastic disease. Genistein, a natural isoflavone product, has anti-tumor properties. Through in vitro and in vivo studies, we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner. In addition, genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner. Furthermore, high concentrations of genistein have no adverse effect on normal esophageal epithelial cells. Mechanistically, genistein treatment strikingly reduced the expression of cell cycle-associated genes, and up-regulated the expression of cell apoptosis-related genes in EsC cells. Additionally, genistein dramatically decreased epidermal growth factor receptor (EGFR) expression and attenuated its down-stream signaling molecules STAT3, MDM2, Akt and JAK1/2 phosphorylation, resulting in inhibited nuclear translocation of STAT3 and MDM2, thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways. In xenograft nude mice, genistein administration strikingly impaired tumor growth in a dose-dependent manner. Moreover, similar disturbances in molecular mechanisms were observed in vivo. Taken together, genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression, leading to cell apoptosis, cell cycle arrest, and proliferation inhibition in EsC cells. Our findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC.

Effects of Ilex latifolia and Camellia sinensis on cholesterol and circulating immune complexes in rats fed with a high-cholesterol diet.

Hypercholesterolaemia is one of the risk factors for atherosclerosis and subsequent cardiovascular disease. Here, we investigated the effects of dietary supplementation with Ilex latifolia or green tea (Camellia sinensis) on the levels of plasma total cholesterol, high-density lipoprotein cholesterol and circulating immune complexes in Sprague Dawley rats fed with a high-cholesterol diet. We demonstrated that daily administration by gavage of I. latifolia or C. sinensis at doses of 1.0 or 2.0 g/kg body weight for 30 days resulted in a significant decrease in plasma total cholesterol levels and circulating immune complexes and an increase in high-density lipoprotein cholesterol in rats fed with a high-cholesterol diet compared with levels in the high-cholesterol diet control group. C. sinensis was more effective than I. latifolia. I. latifolia and C. sinensis could be used as food supplements to protect against the development of hypercholesterolaemia.