title: X609, a novel manassantin A derivative, exhibits antitumor activity in MG-63 human osteosarcoma cells in vitro and in vivo.
abstract: Manassantin A has been well-established as an inhibitor of HIF-1. In the present study, a new manasantin A derivative, X609, with decreased stereochemical complexity, rendering it amenable to a simplified synthesis scheme, was synthesized and was found to increase HIF-1 inhibitory activity. X609 exhibited antiproliferative activity in a broad spectrum of tumor cell lines, via HIF-1-dependent mechanisms. X609 may induce apoptosis in MG-63 cells through activation of the mitochondrial pathway. Oral administration of X609 significantly inhibited the growth of human osteosarcomas implanted into nude mice. In light of the results of the present study, it may be possible to develop X609 for use as a novel antitumor agent, which targets human osteosarcoma.
authors.affiliation: Department of Orthopedics, The Quanzhou Licheng Xingxian Hospital, Quanzhou 362005, P.R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Linyi People's Hospital, Linyi 276000, P.R. China.
authors.forename: Kongbo
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Shandong Provincial Hospital, Jinan 250021, P.R. China.
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Orthopedics, The Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Zongyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017705:Lignans; D019253:Proto-Oncogene Proteins c-bcl-2; C054895:manassantin A; D020169:Caspases; D017239:Paclitaxel