title: Convallatoxin, a dual inducer of autophagy and apoptosis, inhibits angiogenesis in vitro and in vivo.
abstract: Autophagy and apoptosis are important processes that control cellular homeostasis and have been highlighted as promising targets for novel cancer therapies. Here, we identified convallatoxin (CNT), isolated from Antiaris toxicaria, as a dual inducer of autophagy and apoptosis. CNT exerts cytotoxic effects on a number of cancer and normal cell lines and induces apoptosis by increasing caspase-3 and poly ADP ribose polymerase (PARP) cleavage. Moreover, dose- and time-dependent autophagic activity was detected in CNT-treated cells, and mammalian target of rapamycin (mTOR)/p70S6K signal pathway inhibition was observed. Notably, CNT inhibits human umbilical vein endothelial cell (HUVEC) growth and exerts anti-angiogenic activity in vitro and in vivo. Collectively, these results demonstrate that the naturally occurring compound, CNT, is a novel anti-angiogenic compound via dual inducing of autophagy and apoptosis.
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Seung Ya
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Hukeun
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D031621:Antiaris / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D013328:Strophanthins / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D013328:Strophanthins; D058570:TOR Serine-Threonine Kinases; C000505:convallatoxin