title: Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells.
abstract: Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L-1) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Bing-Yu
authors.initials: BY
authors.lastname: Chen
authors.affiliation: Wenzhou Center for Disease Control and Prevention, Wenzhou 325001, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Lyu
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Kai-Qiang
authors.initials: KQ
authors.lastname: Li
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Jiang
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zeng
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: He
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Hou-Quan
authors.initials: HQ
authors.lastname: Tao
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Mou
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: You-Min
authors.initials: YM
authors.lastname: Ying
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China. Electronic address: mmizjpph89@163.com.
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Zhu
authors.affiliation: Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China. Electronic address: zhenwangzjpph@163.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D031101:Marsdenia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D011493:Protein Kinase C
keywords: Angiogenesis; Apoptosis; Cancer; Marsdeniae tenacissimae extraction; Proliferation