Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells

被引:71
作者
Chin, Hsien-Kuo [1 ]
Horng, Chi-Ting [2 ,3 ]
Liu, Yi-Shan [4 ,5 ]
Lu, Chi-Cheng [6 ]
Su, Chen-Ying [7 ]
Chen, Pei-Syuan [8 ]
Chiu, Hong-Yi [6 ]
Tsai, Fuu-Jen [9 ,10 ,11 ]
Shieh, Po-Chuen [8 ]
Yang, Jai-Sing [12 ]
机构
[1] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Kaohsiung 80284, Taiwan
[2] Kaohsiung Armed Forces Gen Hosp, Med Educ Ctr, Kaohsiung 80284, Taiwan
[3] Chung Shan Med Univ, Inst Biochem & Biotechnol, Taichung 40201, Taiwan
[4] E Da Hosp, Dept Dermatol, Kaohsiung 82445, Taiwan
[5] I Shou Univ, Kaohsiung 82445, Taiwan
[6] Buddhist Tzu Chi Gen Hosp, Dept Pharm, Hualien 97002, Taiwan
[7] Tajen Univ, Dept Nursing, Pingtung 90741, Taiwan
[8] Tajen Univ, Dept Pharm, 20 Weixin Rd, Pingtung 90741, Taiwan
[9] China Med Univ Hosp, Dept Med Res, Huamn Genet Ctr, Taichung 40447, Taiwan
[10] China Med Univ Hosp, Dept Med Genet, Taichung 40447, Taiwan
[11] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan
[12] China Med Univ, China Med Univ Hosp, Dept Med Res, 2 Yude Rd, Taichung 40447, Taiwan
关键词
angiogenesis; kaempferol; VEGF receptor-2; AKT; MEK; ERK; human umbilical vein endothelial cells (HUVECs); CANCER STEM-CELLS; NF-KAPPA-B; INDUCED APOPTOSIS; AUTOPHAGY; MIGRATION; THERAPY; MODULATION; ARREST; AKT; CHEMOPREVENTION;
D O I
10.3892/or.2018.6312
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS-mediated p53/ATM/death receptor signaling. However, the anti-angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF-stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF-stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF-stimulated HUVECs. VEGF receptor-2 (VEGFR-2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2-ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF-stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR-2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.
引用
收藏
页码:2351 / 2357
页数:7
相关论文
共 55 条
[1]   Anti-angiogenic treatment in breast cancer: Facts, successes, failures and future perspectives [J].
Aalders, Kim C. ;
Tryfonidis, Konstantinos ;
Senkus, Elbieta ;
Cardoso, Fatima .
CANCER TREATMENT REVIEWS, 2017, 53 :98-110
[2]   Epigallocatechin-3-Gallate: The Prospective Targeting of Cancer Stem Cells and Preventing Metastasis of Chemically-Induced Mammary Cancer in Rats [J].
Abd El-Rahman, Sahar S. ;
Shehab, Gehan ;
Nashaat, Heba .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2017, 354 (01) :54-63
[3]  
Ai B, 2016, AM J CANCER RES, V6, P1624
[4]  
Allegrini G, 2014, PHARMACOGENOMICS, V15, P1985, DOI [10.2217/pgs.14.140, 10.2217/PGS.14.140]
[5]   Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention [J].
Arif, Hussain ;
Sohail, Aamir ;
Farhan, Mohd ;
Rehman, Ahmed Abdur ;
Ahmad, Aamir ;
Nadi, S. M. .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2018, 106 :569-578
[6]   Angiogenesis Modulation-The "Spice Effect" [J].
Bhattacharjee, Shamee ;
Mandal, Deba Prasad .
JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY, 2012, 31 (03) :273-283
[7]   Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human endothelial cells [J].
Che, Jianbo ;
Liang, Bing ;
Zhang, Yuan ;
Wang, Yi ;
Tang, Jianyu ;
Shi, Gongning .
CARDIOVASCULAR PATHOLOGY, 2017, 31 :57-62
[8]   Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer: A systematic review and pooled analysis [J].
Chebib, Ralph ;
Verlingue, Loic ;
Cozic, Nathalie ;
Faron, Matthieu ;
Burtin, Pascal ;
Boige, Valerie ;
Hollebecque, Antoine ;
Malka, David .
SEMINARS IN ONCOLOGY, 2017, 44 (02) :114-128
[9]   A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention [J].
Chen, Allen Y. ;
Chen, Yi Charlie .
FOOD CHEMISTRY, 2013, 138 (04) :2099-2107
[10]   Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells [J].
Chen, Hui-Jye ;
Lin, Chung-Ming ;
Lee, Chao-Ying ;
Shih, Nai-Chen ;
Peng, Shu-Fen ;
Tsuzuki, Minoru ;
Amagaya, Sakae ;
Huang, Wen-Wen ;
Yang, Jai-Sing .
ONCOLOGY REPORTS, 2013, 30 (02) :925-932