title: Proteomic analysis of gossypol induces necrosis in multiple myeloma cells.
abstract: Gossypol is a phenolic aldehyde extracted from plants and is known to be an antitumor agent to induce cancer cell apoptosis. In the present study, multiple myeloma cells were treated with gossypol, which resulted in an increase of cellular reactive oxygen species (ROS) and cell necrosis. Quantitative proteomic analysis was carried out to identify differentially expressed proteins between untreated and gossypol-treated cells. Proteomic analysis identified 4330 proteins, in which 202 proteins are upregulated and 383 proteins are downregulated in gossypol-treated cells as compared to the untreated cells. Importantly, proteomic and western blot analysis showed that apoptosis regulators BAK and Bax were upregulated in gossypol-treated cells, indicating that Bcl-2 associated death pathway was activated. Similarly, gossypol also induced upregulations of DNA mismatch repair proteins and DNA replication licensing factor, suggesting that gossypol caused significant DNA damage. Furthermore, upregulations of HLA class I and class II histocompatibility antigens and beta-2-microglobulin were observed in gossypol-treated cells, indicating that gossypol has a novel function to activate cellular immune responses. Our data demonstrate that the execution of necrosis is a complex process involving ROS, DNA damage, and Bcl-2 family proteins. Gossypol-activated immune responses are a potential new approach for multiple myeloma chemotherapy.
authors.affiliation: Clinical Laboratory of Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China ; Binzhou Medical University, Yantai 264003, China.
authors.forename: Renhua
authors.identifier: 0000-0002-3588-1018
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Nuclear Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
authors.forename: Enbing
authors.initials: E
authors.lastname: Tian
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Tang
authors.affiliation: Clinical Laboratory of Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Chongdong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Clinical Laboratory of Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D009336:Necrosis; D009363:Neoplasm Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D006072:Gossypol