title: Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6.
abstract: This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Fan-Cong
authors.initials: FC
authors.lastname: Kong
authors.affiliation: Department of Oncology, Wuhan Central Hospital, Wuhan, 430012, China.
authors.forename: Jing-Qiong
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Ren
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Yan
authors.affiliation: Department of Hematology, Wuhan Central Hospital, Wuhan, 430012, China.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. doctorlee007@sina.com.
authors.forename: Qiu-Bai
authors.initials: QB
authors.lastname: Li
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. chenzhichao@hust.edu.cn.
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000097:blood; D012717:Sesquiterpenes / Q000494:pharmacology*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D016328:NF-kappa B; C498143:RELA protein, human; D012717:Sesquiterpenes; D048029:TNF Receptor-Associated Factor 6; D051996:Transcription Factor RelA; C002669:parthenolide