title: Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.
abstract: Resistance to chemotherapy is a great challenge to improving the survival of patients with diffuse large B-cell lymphoma (DLBCL), especially those with activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule derived from Chinese herb gamboges, has been approved for Phase II clinical trial for cancer therapy by Chinese FDA. In the present study, we investigated the effect of GA on cell survival and apoptosis in DLBCL cells including both GCB- and ABC-DLBCL cells. We found that GA induced growth inhibition and apoptosis of both GCB- and ABC-DLBCL cells in vitro and in vivo, which is associated with proteasome malfunction. These findings provide significant pre-clinical evidence for potential usage of GA in DLBCL therapy particularly in ABC-DLBCL treatment.
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Xianping
authors: X
authors: Shi
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Xiaoying
authors: X
authors: Lan
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Xin
authors: X
authors: Chen
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Chong
authors: C
authors: Zhao
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Xiaofen
authors: X
authors: Li
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Shouting
authors: S
authors: Liu
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Hongbiao
authors: H
authors: Huang
authors: 1] State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China [2] Guangzhou Research Institute of Cardiovascular Disease, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors: Ningning
authors: N
authors: Liu
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Dan
authors: D
authors: Zang
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Yuning
authors: Y
authors: Liao
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Peiquan
authors: P
authors: Zhang
authors: 1] State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China [2] Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota 57069, USA.
authors: Xuejun
authors: X
authors: Wang
authors: State Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Departments of Pathophysiology and Biochemistry, Guangzhou Medical University, Guangdong 510182, China.
authors: Jinbao
authors: J
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D061988:Proteasome Inhibitors; D044004:Xanthones; C052659:gambogic acid; D020169:Caspases; D046988:Proteasome Endopeptidase Complex