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| Celastrus Orbiculatus Extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in Vitro and in Vivo |
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| Author Name | Affiliation | E-mail | | Ya-yun Qian | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China | | | Hua Zhang | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China | | | Ying Hou | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China | | | Lin Yuan | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China
Department of Image, 97th Hospital of People’s Liberation Army, Xuzhou, Jiangsu Province, 221000, China | | | Guo-qing Li | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China | | | Shi-yu Guo | Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Tokyo, 142-8555, Japan | | | Tadashi Hisamits | Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Tokyo, 142-8555, Japan | | | Yan-qing Liu | Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China | liuyq@yzu.edu.cn |
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| Abstract: |
Objective Celastrus orbiculatus Thunb. has been used for thousands of years in China as a remedy against cancer and inflammatory diseases. This study aims to investigate whether C. orbiculatus extract (COE) could inhibit angiogenesis, which is the pivotal step in tumor growth, invasiveness, and metastasis. Methods In this study, the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10, 20, 40, 80, and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any antiangiogenic effects. Results COE significantly inhibited proliferation and induced apoptosis in Hepa1-6 cells and inhibited VEGF expression at both mRNA and protein levels. Furthermore, this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo, COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis. Conclusions In summary, COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein. |
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