title: Small compound bigelovin exerts inhibitory effects and triggers proteolysis of E2F1 in multiple myeloma cells.
abstract: Multiple myeloma (MM) is a currently incurable blood cancer. Here we tested the effects of a small compound bigelovin on MM cells, and reported that it caused cell cycle arrest and subsequently induced apoptosis. Bigelovin triggered proteolysis of E2F1, which could be inhibited by caspase inhibitor. To investigate the clinical relevance, the expression of E2F1 in MM specimens was tested, and the results showed that E2F1 was overexpressed in 25-57% of MM patients and was associated with higher International Staging System (ISS) stage. These results suggest that E2F1 may be important for MM pathogenesis, and bigelovin could serve as a lead compound for the development of E2F1 inhibitor.
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, Guangzhou Institutes of Biomedicine and Health & State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Science and Technology of China, Hefei, China.
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Liu
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Zeng
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Liu
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Liu
authors.forename: Zhong-Guo
authors.initials: ZG
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ning-Hua
authors.initials: NH
authors.lastname: Tan
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D007783:Lactones; D034741:RNA, Small Interfering; D012717:Sesquiterpenes; C099796:bigelovin