Xiufeng Pang
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Zhengfang Yi
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Xiaoli Zhang
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Bokyung Sung
Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Weijing Qu
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Xiaoyuan Lian
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Bharat Aggarwal
Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Mingyao Liu
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
The role of angiogenesis in tumor growth and metastasis is well established. Identification of small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we demonstrated that acetyl-11-keto-β-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg of AKBA) after solid tumors reached about 100 mm3 (n=5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively and suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 kinase (KDR/Flk-1) with IC50 of 1.68 μmol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mTOR, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways.
Keywords: AKBA, KDR/Flk-1, tumor angiogenesis, mTOR, prostate tumor
Author Biographies
Xiufeng Pang, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas
Mingyao Liu, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas
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