Objectives: Cardiomyocyte hypertrophy is an important structural feature of diabetic cardiomyopathy. Calcineurin/nuclear factor of activated T-cell (NFAT) pathway plays a central role in the pathogenesis of cardiac hypertrophy. The purpose of this study was to investigate the effects of tropisetron, a novel calcineurin inhibitor, on high glucose (HG)-induced cardiomyocyte hypertrophy and its underlying mechanism. Methods: H9c2 myocardial cells were treated with tropisetron or cyclosporine A 1 h before exposure to HG for 48 h. Key findings: Exposure to HG resulted in enhanced cell size, protein content and atrial natriuretic peptide (ANP) protein expression. HG significantly increased Ca2+ level, calcineurin expression and nuclear translocation of NFATc4. Both tropisetron and cyclosporine A markedly prevented the hypertrophic characteristic features, calcineurin overexpression and nuclear localization of NFATc4 while intracellular Ca2+ was not affected. Conclusion: Our results showed that tropisetron may have protective effects against HG-induced cardiomyocyte hypertrophy. The mechanism responsible for this beneficial effect seems to be, at least in part, blockade of calcineurin/NFAT signalling pathway.

Xanthomicrol, a trimethoxylated hydroxyflavone, is the main active component of Dracocephalum kotschyi Boiss leaf extract. Preliminary in vitro studies identified this compound as a potential antiangiogenic and anticancer agent. This study aimed to evaluate in vivo anticancer effect of xanthomicrol and investigate its molecular mechanism of action in a mouse melanoma (B16F10) model. Effect of xanthomicrol on B16F10 melanoma cell viability was determined using the MTT assay. For in vivo experiments, C57BL/6 mice were inoculated subcutaneously with B16F10 cells. After five days, once daily administration of xanthomicrol, thalidomide, or vehicle was commenced and continued for 21 consecutive days. On the 26th day, blood samples and tumor biopsies were taken for subsequent molecular analysis. Xanthomicrol showed inhibitory effect on viability of B16F10 melanoma cells (IC50 value: 3.433 μg/ml). Initial tumor growth, tumor volume and weight, and angiogenesis were significantly decreased in xanthomicrol‐treated animals compared with those in vehicle group. Protein expression of phosphorylated Akt, mRNA expressions of HIF‐1α and VEGF in tumor tissues, and serum VEGF were significantly decreased in xanthomicrol‐treated animals compared with vehicle‐treated animals. Thus, xanthomicrol inhibited cancer cell growth both in vitro and in vivo. This effect, at least in part, was exerted by interfering with PI3K/Akt signaling pathway and inhibiting VEGF secretion by tumor cells. Further studies are required to elucidate the exact molecular mechanisms of antitumor activity of xanthomicrol.