Subcellular proteome analysis of camptothecin analogue NSC606985-treated acute myeloid leukemic cells.
We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase Cdelta. Here, we analyzed protein expression profiles of fractionated nuclei, mitochondria, raw endoplasmic reticula, and cytosols of NSC606985-induced apoptotic AML cell line NB4 cells by two-dimensional electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry. In total, 90 unique deregulated proteins, including 16 compartment-compartment translocated ones, were identified. They contributed to multiple functional activities such as DNA damage repairing, chromosome assembly, mRNA processing, biosynthesis, modification, and degradation of proteins. More interestingly, several increased oxidative stress-related proteins mainly presented in mitochondria, while upregulated glycolysis proteins mainly occurred in the nuclei. With their functional analyses, the possible roles of these deregulated proteins in NSC606985-induced apoptosis were discussed. Collectively, these discoveries would shed new insights for systematically understanding the mechanisms of the camptothecin-induced apoptosis.
Yu
Yun
Y
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wang
Li-Shun
LS
Shen
Shao-Ming
SM
Xia
Li
L
Zhang
Lei
L
Zhu
Yuan-Shan
YS
Chen
Guo-Qiang
GQ
D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D013347:Subcellular Fractions / Q000378:metabolism
C514334:NSC606985; D020543:Proteome; D051745:Protein Kinase C-delta; D002166:Camptothecin