asiatic acid inhibits pro-angiogenic effects of vegf and human gliomas in endothelial cell culture models亚细亚酸抑制pro-angiogenic vegf的影响和人类神经胶质瘤在内皮细胞培养模型.pdfVIP

Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models 1 1,2 1,2 1,2 Chandagirikoppal V. Kavitha , Chapla Agarwal , Rajesh Agarwal , Gagan Deep * 1 Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Denver, Colorado, United States of America, 2 University of Colorado Cancer Center, Aurora, Colorado, United States of America Abstract Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 mM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected