Anticancer and anti-angiogenic activities of extract from Actinidia eriantha Benth root.
BACKGROUND
The roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously.


OBJECTIVE
This work was carried out to investigate the anticancer and anti-angiogenic activities of AER.


METHODS
The growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A. eriantha on human gastric carcinoma SGC7901 cells, human nasopharyngeal carcinoma CNE2 cells, human breast carcinoma MCF7 cells and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The ethyl acetate fraction from EER (EA-EER) was further investigated for the anticancer activity against SGC7901 cells and the anti-angiogenic activity in HUVECs in vitro. The apoptosis in SGC7901 cells and HUVECs was confirmed by DAPI nuclear staining and flow cytometry analysis, the effect on cellular DNA fragmentation was detected in SGC7901 cells. And the cell cycle-arresting activity in HUVECs was determined by flow cytometry. Moreover, the inhibitory effect of EA-EER on cell migration in HUVECs was observed by both wound-healing and Transwell migration assays. RT-PCR and Western-blotting were performed to determine the mRNA and protein expression levels, respectively, including Bax, Bcl-2 and caspase-3 in SGC7901 cells, as well as VEGF-A and VEGFR-2 in HUVECs. Furthermore, the in vivo anti-angiogenic activity of EA-EER was evaluated by using chick embryo chorioallantoic membrane (CAM) assay. Ultimately, the chemical components in EA-EER were isolated and purified by repeated column chromatography followed by structure characterization using1H and13C nuclear magnetic resonance and mass spectroscopy.


RESULTS
Compared with EEL and EES, EER displayed the strongest growth inhibitory effect on SGC7901 cells, CNE2 cells and HUVECs. Among the EER fractions, EA-EER exhibited the most potent growth inhibitory activity against SGC7901 cells, CNE2 cells and HUVECs. Moreover, EA-EER induced obvious apoptosis in SGC7901 and HUVECs, and significantly inhibited the proliferation of HUVECs via blockade of cell cycle G1 to S progression. Furthermore, EA-EER suppressed the expression of Bcl-2 and improved the expression Bax and caspase-3 in SGC7901 cells. EA-EER not only inhibited migration of HUVECs, but also down-regulated the expression of VEGF-A and VEGFR-2 in HUVECs. In vivo, EA-EER exposure reduced the formation of blood vessels in chick embryos. A bio-guided isolation of EA-EER led to the isolation of three compounds for the first time, namely (6R, 7E, 9S)-6, 9-hydroxy-megastigman-4, 7-dien-3-one-9-O-β-D-glucopyranoside, Oleanolic acid-23-O-β-D-glucopyranoside, 3β, 23, 24-trihydroxyl-12-oleanen-28-oic acid.


CONCLUSIONS
The present research demonstrated that the significant anticancer and anti-angiogenic effects of AER, providing the supportive evidence for its traditional use in the treatment for cancer. It was suggested that AER could be use as a potential source of cancer therapeutic drug.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, NO.1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou 350108, PR China. Electronic address: wjg1419@126.com.
Jian-Guo
JG
Wu
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, NO.1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou 350108, PR China. Electronic address: 374579304@qq.com.
Li
L
Ma
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, NO.1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou 350108, PR China. Electronic address: 280204099@qq.com.
Shui-Hua
SH
Lin
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, NO.1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou 350108, PR China. Electronic address: 122810146@qq.com.
Yan-Bin
YB
Wu
Department of Chemistry and Life Science, Fujian Institute of Education, Fuzhou 350001, PR China. Electronic address: 864741148@qq.com.
Jun
J
Yi
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, PR China. Electronic address: 845725483@qq.com.
Bin-Jun
BJ
Yang
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, NO.1 Qiuyang Road, Shangjie Town, Minhou County, Fuzhou 350108, PR China. Electronic address: jinzhongfj@126.com.
Jin-Zhong
JZ
Wu
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China. Electronic address: kahing.wong@polyu.edu.hk.
Ka-Hing
KH
Wong
D029042:Actinidia / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D018517:Plant Roots; D018547:Plant Stems
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
Actinidia eriantha Benth; Anti-angiogenic; Anti-cancer; Chemical components; Root