Antiangiogenic and antihepatocellular carcinoma activities of the Juniperus chinensis extract

BMC Complementary and Alternative Medicine

Research Article

Ching-Huai Ko¹  I-Huang Lu¹  Mei-Wei Lin¹  Hsin-Chieh Wu¹  Jui-Hung Yen¹  Hsin-Jan Yao¹  Si-Yuan Wu¹  Chun-Chung Wang¹  Shu-Jiau Chiou¹  Yi-Cheng Cheng¹  Zong-Keng Kuo¹  Shyh-Horng Lin¹  Hsiang-Wen Tseng²  I-Horng Pan²  Tien-Soung Tong³ 

[1] Center of Excellence for Drug Development, Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, No. 321, Sec 2, Kuangfu Rd, 30011, Hsinchu City, Taiwan;Center of Excellence for Drug Development, Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, No. 321, Sec 2, Kuangfu Rd, 30011, Hsinchu City, Taiwan;Present address: Bldg 13, No. 321, Sec 2, Kuangfu Rd, 30011, Hsinchu City, Taiwan;Greenhouse System Technology Center, Industrial Technology Research Institute, Central Region Campus, No.2 Wenxian Rd., 54041, Nantou City, Taiwan;

关键词: Juniperus chinensis;    Hepatocellular carcinoma;    Antiangiogenesis;    Therapeutic agent;   

DOI  :  10.1186/s12906-016-1250-6

 received in 2015-09-17, accepted in 2016-07-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundTo identify a novel therapeutic agent for hepatocellular carcinoma (HCC), for which no promising therapeutic agent exists, we screened a panel of plants and found that Juniperus chinensis exhibited potential antiangiogenic and anti-HCC activities. We further investigated the antiangiogenic and anti-HCC effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in vitro and in vivo.MethodsA tube formation assay conducted using human umbilical vein endothelial cells (HUVECs) was first performed to identify the active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous and orthotopic mouse model of HCC. In vitro studies were performed to investigate the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells. Moreover, protein arrays for angiogenesis and apoptosis were used to discover biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7.ResultsCBT-143-S-F6F7 showed significantly antiangiogenic activity in various assays, including HUVEC tube formation and migration, CAM, and Matrigel plug assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice, and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 % increase in median survival duration compared with the vehicle-treated mice). Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7-treated mice showed a significantly decrease in the cell cycle regulatory protein cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT-143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis, possibly contributing to the inhibition of HCC tumors. Protein array analysis revealed that several angiogenic and antiapoptotic factors were suppressed in CBT-143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were identified.ConclusionsAccording to these results, we report for the first time the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants further evaluation as a new anti-HCC drug.

【 授权许可】

CC BY   
© The Author(s). 2016