期刊
FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.806091
关键词
sempervirine; wnt /beta-catenin; alkaloids; Gelsemium elegans benth; hepatocellular carcinoma
资金
- National Natural Science Foundation of China [82000554, 81973309]
- Natural Science Foundation of Fujian Province [2019J01303, 2020J01640, 2020J01618]
- Science and Technology Project of Fujian Province [2018Y2001]
- Research Initiation Fund for High-level Talents of Fujian Medical University [XRCZX2018015]
- Startup Fund of Fujian Medical University [2018QH1015]
- Joint Funds for the Innovation of Science and Technology, Fujian Province [2018Y9075, 2019Y9009]
- Open Project Fund of Fujian Provincial Key Laboratory of Environment Factors and Cancer [GWSZD-202003]
Gelsemium elegans, a toxic plant used in traditional Chinese medicine, showed anti-tumor effects in hepatocellular carcinoma (HCC) through the alkaloid compound sempervirine which induced apoptosis, cell cycle arrest in G(1) phase, and inactivation of the Wnt/beta-catenin pathway.
Gelsemium elegans (G. elegans) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G(1) phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2. Furthermore, sempervirine inhibited HCC tumor growth and enhances the anti-tumor effect of sorafenib in vivo. In addition, inactivation of Wnt/beta-catenin pathway was found to be involved in sempervirine-induced HCC proliferation. The present study demonstrated that alkaloids of G. elegans were a valuable source of active compounds with anti-tumor activity. Our findings justified that the active compound sempervirine inhibited proliferation and induced apoptosis in HCC by regulating Wnt/beta-catenin pathway.
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