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BioMed Research International
Volume 2014 (2014), Article ID 839232, 9 pages
http://dx.doi.org/10.1155/2014/839232
Research Article

Proteomic Analysis of Gossypol Induces Necrosis in Multiple Myeloma Cells

1Clinical Laboratory of Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
2Binzhou Medical University, Yantai 264003, China
3Department of Nuclear Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
4School of Life Sciences, Tsinghua University, Beijing 100084, China

Received 5 June 2014; Accepted 20 July 2014; Published 14 August 2014

Academic Editor: Haiteng Deng

Copyright © 2014 Renhua Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.