title: Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis.
abstract: Angiogenesis is associated with the progression of multiple myeloma (MM). Wogonin is an active mono-flavonoid with remarkable antitumor activity. However, its impact on MM-stimulated angiogenesis remains largely unknown. Here, we demonstrated that wogonin decreased expression and secretion of pro-angiogenic factors in MM cells via c-Myc/HIF-1α signaling axis, reducing MM-stimulated angiogenesis and MM cell proliferation in vivo. Overexpression of c-Myc in MM cells disrupted the balance between VHL SUMOylation and ubiquitination, and thus inhibited proteasome-mediated HIF-1α degradation. Impaired function of VHL ubiquitination complex in c-Myc-overexpressing cells was fully reversed by wogonin treatment via increasing HIF-1α-VHL interaction and promoting HIF-1α degradation. Collectively, our in vitro and in vivo studies reveal for the first time that wogonin represses MM-stimulated angiogenesis and tumor progression via c-Myc/VHL/HIF-1α signaling axis.
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Teng
authors.initials: T
authors.lastname: An
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing 211189, China.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
authors.affiliation: Department of Physiology, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhao-Qiu
authors.initials: ZQ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D044950:Flavanones; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C085514:wogonin
keywords: VHL; angiogenesis; c-Myc; multiple myeloma; wogonin