Dioscin inhibits the growth of human osteosarcoma by inducing G2/M-phase arrest, apoptosis, and GSDME-dependent cell death in vitro and in vivo.

Pyroptosis is a form of programmed cell death (PCD) that plays a vital role in immunity and diseases. Although it was recently reported that chemotherapy drugs can induce pyroptosis through caspase-3-dependent cleavage of gasdermin E (GSDME), the role of pyroptosis in osteosarcoma (OS) with dioscin is less understood. In this study, we explored the effects of dioscin on OS in vitro and in vivo and further elucidated the underlying molecular mechanisms and found that dioscin-triggered pyroptosis in GSDME-dependent cell death and that GSDME-N was generated by caspase-3. Furthermore, dioscin inhibited cancer cell growth by inducing G2/M arrest and apoptosis through the JNK/p38 pathway. In vivo, dioscin significantly inhibited OS proliferation. Taken together, our results demonstrate that dioscin can induce apoptosis through the JNK/p38 pathway and GSDME-dependent pyroptosis in OS, identifying it as a potential therapeutic drug for treatment of this disease.

A novel treatment strategy in hepatocellular carcinoma by down-regulation of histone deacetylase 1 expression using a shRNA lentiviral system.

Up to now, effective treatment methods for hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, have remained very limited. Previous studies have shown that histone deacetylase 1 (HDAC1) is highly expressed in HCC. The adoption of HDAC inhibitors in HCC treatment has also been studied, however, only moderate efficacy was observed. In the current study, using a clinically approved shRNA lentiviral system, we investigated whether the down-regulation of HDAC1 on mRNA level could suppress HCC progression. Our results showed that HDAC1 shRNA lentivirus infection could significantly reduce HCC Hep3B cell viability but have little impact on normal liver cell THLE-3. Cell cycle analysis revealed that HDAC1 shRNA lentivirus treatment could arrest HCC cells at G1 phase, which was probably achieved by modulating expression of cell cycle-related proteins including Cyclin D1, p21 and p27. Invasion assay showed that HDAC1 knock-down could dramatically reduce the invasiveness of HCC cells, which was correlated to the altered expression of some epithelial-mesenchymal transition related proteins including ZO-1, E-cadherin and Vimentin. Taken together, our findings have shown that down-regulation of HDAC1 on mRNA level using shRNA lentiviral system might be a novel alternative treatment strategy for HCC.