Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1-RAGE and AKT pathways.

Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1-RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

Cheng P ，Dai W ，Wang F ，Lu J ，Shen M ，Chen K ，Li J ，Zhang Y ，Wang C ，Yang J ，Zhu R ，Zhang H ，Zheng Y ，Guo CY ，Xu L ... -  《-》

Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo.

Zhang J ，Zhu JS ，Zhou Z ，Chen WX ，Chen NW ... -  《-》

Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis.

Li ML ，Wang XF ，Tan ZJ ，Dong P ，Gu J ，Lu JH ，Wu XS ，Zhang L ，Ding QC ，Wu WG ，Rao LH ，Mu JS ，Yang JH ，Weng H ，Ding Q ，Zhang WJ ，Chen L ，Liu YB ... -  《INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY》

Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis.

Wang X ，Bai H ，Zhang X ，Liu J ，Cao P ，Liao N ，Zhang W ，Wang Z ，Hai C ... -  《-》

Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis.

Zhao J ，Chen X ，Lin W ，Wu G ，Zhuang Q ，Zhong X ，Hong Z ，Peng J ... -  《-》