Combination effects of salvianolic acid B with low-dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo.

Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development.

Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways.

Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long-term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC(50) of 18 and 50 microM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80 mg/kg/day) or celecoxib (5 mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p < 0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E(2) synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment.

[Expression changes of nitric oxide synthase mRNA of hypothalamus after sleep deprivation in rats].

OBJECTIVE: To study the effects of rapid eye movement sleep (REMS) deprivation on the expression of mRNA coding for neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) of hypothalamus in rats. METHOD: Flower pot technique was adopted to deprive the REMS of Sprague-Dawley rats for 24 h, 48 h and 72 h respectively. The expression of mRNA coding for nNOS or iNOS of hypothalamus in rats was assayed by reverse-transcription polymerase chain reaction (RT-PCR). RESULT: The amount of nNOS mRNA was significantly higher in 24 h REMS deprivation group (P<0.01), then the amount was lowered in 48 h deprivation group and became significantly lower in 72 h deprivation group than that in the control group (P<0.05). There was low expression of iNOS mRNA of hypothalamus in rats, and there was no difference in the expression of iNOS mRNA among 24 h, 48 h REMS deprivation and the control groups. But the expression was significantly increased in 72 h REMS deprivation group (P<0.01). CONCLUSION: Deprivation of REMS increased the expression of nNOS and iNOS mRNA of hypothalamus. Excessive nitric oxide (NO) might be a major factor resulting in not only the sleep rebound phenomenon but also the injury of human function caused by sleep loss directly or indirectly by other sleep factors.

Carbohydrate loading and supplementation in endurance-trained women runners.

The purpose of this study was to examine the effect of carbohydrate (CHO) augmentation on endurance performance and substrate utilization in aerobically trained women. Eight endurance-trained women completed a 24.2-km (15 mile) self-paced treadmill performance run under three conditions: CHO supplementation (S), CHO loading and supplementation (L+S), and placebo (P). Dietary CHO was approximately 75% of energy intake for L+S and approximately 50% for both S and P. A 6% CHO-electrolyte solution (S and L+S) or placebo (P) was ingested preexercise (6 ml/kg) and every 20 min during exercise (3 ml/kg). Blood glucose was significantly higher at 40, 60, and 100 min during L+S, and at 60, 80, and 100 min during S compared with P (P < 0.05). Blood lactate was significantly higher (P < 0.05) during L+S than S and P. Blood glycerol was significantly lower (P < 0.05) at 20, 80, and 100 min during L+S, and at 80 and 100 min during S than P. The proportion of CHO (%) utilized during exercise was significantly higher (P < 0.05) during L+S (71.3 +/- 3.8%) and S (67.3 +/- 4.3%) than P (59.2 +/- 4.6%). Performance times (P > 0.05) were 132.5 +/- 6.3 min (S), 134.4 +/- 6.3 min (L+S), and 136.6 +/- 7.9 min (P). In conclusion, it appears that when CHO availability in women is increased through CHO loading and/or CHO supplementation, there is a concomitant increase in CHO utilization. However, this may not necessarily result in significantly improved performance.