dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through inhibition of aktgsk-3β and mtor signaling pathwaysdehydrocostuslactone体外和体内通过抑制血管生成抑制aktgsk-3βmtor信号通路.pdfVIP

Dehydrocostuslactone Suppresses Angiogenesis In Vitro and In Vivo through Inhibition of Akt/GSK-3b and mTOR Signaling Pathways 1 2 3,4 1 5,6 1 . Chih-Ya Wang , An-Chi Tsai , Chieh-Yu Peng , Ya-Ling Chang , Kuo-Hsiung Lee , Che-Ming Teng * , Shiow-Lin Pan2*. 1 Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, 2 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Taiwan, 3 Natural Medicinal Products Research Center, China Medical University Hospital, Taichung, Taiwan, 4 Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, 5 Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, United States of America, 6 Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan Abstract The traditional Chinese medicine component dehydrocostuslactone (DHC) isolated from Saussurea costus (Falc.) Lipschitz, has been shown to have anti-cancer activity. Angiogenesis is an essential process in the growth and progression of cancer. In this study, we demonstrated, for the first time, the anti-angiogenic mechanism of action of DHC to be via the induction of cell cycle progression at the G0/G1 phase due to abrogation of the Akt/glycogen synthase kinase-3b (GSK-3b)/cyclin D1 and mTOR signaling pathway. First, we demonstrated that DHC has an anti-angiogenic effect in the matrigel-plug nude mice model and an inhibitory effect on human umbilical vein endothelial cell (HUVEC) proliferation and capillary-like tube formation in vitro. DHC c