Ceramide production mediates cinobufotalin-induced growth inhibition and apoptosis in cultured hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal neoplasm with poor prognosis. The aim of this study is to investigate the anticancer activity of cinobufotalin, a bufadienolide isolated from toad venom, in cultured HCC cells, and to study the underlying mechanisms. We found that cinobufotalin (at nmol/L) significantly inhibited HCC cell growth and survival while inducing considerable cell apoptosis. Further, cinobufotalin inhibited sphingosine kinase 1 (SphK1) activity and induced pro-apoptotic ceramide production. Ceramide synthase-1 small hairpin RNA (shRNA)-depletion inhibited cinobufotalin-induced ceramide production and HCC cell apoptosis. On the other hand, the glucosylceramide synthase (GCS) inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitated cinobufotalin-induced ceramide production and cell apoptosis. SphK1 inhibitor II (SKI-II), similar to cinobufotalin, increased cellular ceramide level and promoted HCC cell apoptosis. Finally, we observed that cinobufotalin inactivated Akt-S6K1 signaling in HepG2 cells, which was again inhibited by ceramide synthase-1 shRNA-depletion. In conclusion, the results of this study suggest that cinobufotalin induces growth inhibition and apoptosis in cultured HCC cells through ceramide production. Cinobufotalin may be investigated as a novel anti-HCC agent.

[Study of Fermi resonance by means of solution concentration variation].

The values of Raman scattering coefficients of some molecules in which Fermi resonance occurs vary with solution concentration variation. We measured the Raman spectra of some solvents such as CCl4, CS2, C6H6, etc by changing the concentration of the solutions ranging from 10% to 100% in volume. As a result, the authors obtained the general law of Fermi resonance. We found some weak Fermi resonance phenomena as well that the two bands of Raman spectrum shift asymmetrically and that the fundamental of overtone is tuned by Fermi resonance and moves towards the same direction with the overtone simultaneously, which is same as the results Bier K. D. obtained by means of high-pressure technique. By means of this method, the authors demonstrated the conclusion that only the fundamental in combinations which has the same symmetry as the fundamental involved in Fermi resonance directly can its intensity variation influence the Fermi resonance. In this article, the authors present a new method to study Fermi resonance. This method is valuable in the identification and the assignment of spectral lines of solutions, the determination of molecular configuration of enzyme, the discrimination of isomer, as well as the influences on the molecular structures and properties caused by hydrogen bond.

Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model.

AIMS: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. METHODS: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. RESULTS: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. CONCLUSION: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions.