ABSTRACT
Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.
ABSTRACT
This study examined whether genistein influences the production of nitric oxide (NO) and expression of endothelial nitric oxide synthase (eNOS) and the modulators of eNOS activity in ovariectomized (OVX) rat hearts. Female mature Sprague-Dawley rats were subjected to bilateral ovariectomy, OVX rats were randomly divided into four groups: 17beta-estradiol (0.1 mg/kg, s.c. daily) was used as the positive control; low dose of genistein (0.5 mg/kg, s.c. daily); high dose of genistein (5.0 mg/kg, s.c. daily) and model. Sham operations as controls, the treatment lasted 6 weeks. Blood pressure, heart rate, plasma estradiol, heart and uterine weights were measured. Nitrite production in the myocardium was determined by nitrate reductase method. Protein level of eNOS, caveolin-1 and calmodulin was determined by Western blot. The results showed that nitrite production and eNOS protein in homogenized ventricular tissue was attenuated by approximately 53% and 67% in OVX rats compared with those in sham rats, respectively. Genistein increased nitrite production in rat heart in a dose-dependent manner, genistein at the dose of 5 mg/kg.d(-1) resumed nitrite production to a level similar to that in sham operated rats. Administration of genistein also increased eNOS protein expression in OVX rats myocardium with a concomitant decrease in the expression of caveolin-1, an endogenous eNOS inhibitory protein. Another eNOS stimulatory protein, calmodulin, was unchanged in these treatments. These effects were also observed in rats treated with 17beta-estradiol. Genistein at the dose of 5.0 mg/kg.d(-1) augmented uterine weight but this side effect in reproductive system was less than that of 17beta-estradiol. These results suggest that genistein supplementation and estrogen replacement therapy directly increase eNOS functional activity and NO production in the hearts of the OVX rats, but genistein has less side effects on the reproductive system than 17beta-estradiol.