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Anti-liver cancer effect of polyphyllin VII and its molecular mechanisms

English Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Liver transplantation and surgical resection are the most efficient therapeutic strategies for early stage of HCC. However, current conventional therapies are still not effective to treat patients of advanced HCC. Hence, it is imperative to develop novel therapeutic drugs with high efficiency and low toxicity for HCC. In recent years, traditional Chinese medicine has been increasingly applied in HCC prevention and treatment due to the advantages of safety and lower drug resistance. Paris polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activities. However, the underlying mechanisms are poorly understood and no further study continues focusing on this area in vivo. Furthermore, the antiangiogenic and anti-metastatic effects of PP7 have not been evaluated yet. Therefore, the present study aims to explore the potential effect of PP7 on liver cancer. Our study demonstrates that PP7 induces apoptotic cell death in HepG2 cells through both intrinsic and extrinsic pathways by promoting the generation of mitochondrialmediated ROS and activating MAPK and PTEN/p53 pathways. Furthermore, PP7 induces an autophagic cell death in HepG2 cells via inhibition of PI3K/AKT/mTOR, and activation of JNK pathway, which induces phosphorylation of Bcl-2 and iv dissociation of Beclin-1 from Beclin-1/Bcl-2 complex, leading to induction of autophagy. Moreover, PP7 has dual biological activities i.e inhibiting blood vessel development and at the same time suppressing the growth and metastasis of zebrafish xenografts. Additionally, PP7 treatment could significantly inhibit hepatocellular carcinoma growth in mice and prolong the survival time of tumor-bearing mice and inhibit lung metastases of H22 in mice. Immunohistochemistry staining of the tumor tissues results shows that PP7 inhibits cancer cell proliferation and tumor angiogenesis, and induces apoptosis of cancer cells. Finally, our study also showed that PP7 possessed potent anti-inflammatory activity against inflammation in vitro and in vivo. Based on the scientific work we carried out and the achievements mentioned above, we conclude that the anti-cancer profile of PP7 is promising and further studies are needed to potentiate PP7 as an anti-cancer agent.

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Zhang, Chao


Institute of Chinese Medical Sciences




Liver -- Diseases -- Treatment

Medicinal plants -- China




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