Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway
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Zhongping Fu1,2,5,*, Xiao Chen2,*, Shengwen Guan2,3,4, Yanju Yan4, Huan Lin5, Zi-Chun Hua1,2,6
1State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China
2The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
3Nanjing Industrial Innovation Center for Pharmaceutical Biotechnology, Nanjing, Jiangsu, China
4Changzhou High-Tech Research Institute of Nanjing University and Targetpharma Laboratory, Changzhou, Jiangsu, China
5Jiangsu Simcere Pharmaceutical R&D Co., Ltd., Nanjing, China
6College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
*These authors have contributed equally to this work
Zi-Chun Hua, e-mail: [email protected]
Keywords: curcumin, angiogenesis, VEGF, anemia, extramedullary hematopoiesis
Received: January 02, 2015 Accepted: April 25, 2015 Published: August 14, 2015
Curcumin, a natural polyphenol compound from the perennial herb Curcuma longa, has been proved to be beneficial for tumor-bearing animals through inhibiting tumor neovasculature formation, but the underlying mechanisms are unclear. Here, we aim to test whether curcumin affects VEGF-VEGFR2 signaling pathway and attenuates defective hematopoiesis induced by VEGF in tumor model. We demonstrated that curcumin inhibited proliferation, migration of HUVEC under VEGF stimulation and caused HUVEC apoptosis, and blocked VEGFR2 activation and its downstream signaling pathways in vitro. Furthermore, in VEGF over-expressing tumor model, curcumin significantly inhibited the tumor growth accelerated by VEGF in a dose-dependent manner and improved anemia and extramedullary hematopoiesis in livers and spleens of tumor-bearing mice induced by tumor-derived VEGF. Immunohistochemical analysis showed that curcumin normalized vasculature structures of livers and reduced tumor microvessel density. ELISA revealed that curcumin suppressed VEGF secretion from tumor cells both in vitro and in vivo. Survival analysis showed that curcumin significantly improved survival ability of VEGF tumor-bearing mice. Taken together, these findings establish curcumin as a modulator of VEGF and VEGF-VEGFR2 signaling pathway, with potential implication for improving the quality of life of cancer patients.
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