Prohibitin promotes apoptosis of promyelocytic leukemia induced by arsenic sulfide.
Arsenic sulfide (As4S4), an oral form of arsenic agent, has been shown to have similar efficacy and safety to intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia (APL). The aim of the present study was to identify proteins modulated by As4S4 and to determine their involvement in the apoptotic pathway. We used comparative proteomic analysis to screen and identify the proteins that were differentially expressed with As4S4 treatment. Prohibitin (PHB) was selected for its diverse role and its increased expression in the cells treated with As4S4. To examine whether PHB play a functional role, two clones of PHB-knockdown and PHB-overexpression were generated by transfection of NB4-R1 with vectors containing PHB gene sequences. In comparison with parental NB4-R1 cells, PHB overexpression showed an increase in baseline apoptosis and an enhanced response in As4S4-induced apoptosis. PML-RARα fusion protein was found to be reduced with PHB-overexpression, and following As4S4 treatment, a greater reduction of promyelocytic leukemia-retinoic acid receptor-α (PML-RARα) fusion protein was seen in PHB-overexpression than that in parental cells. Consistently, PHB knockdown presented with a significant reduction in As4S4-induced apoptosis and a lesser degree of PML-RARα degradation. The results indicate the antitumor activity of PHB in promoting apoptosis of APL cells.
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Pengcheng
P
He
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Yanfeng
Y
Liu
Institute of Xi'an Blood Bank, Shaanxi Blood Center, Xi'an, Shaanxi, P.R. China.
Jun
J
Qi
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Huachao
H
Zhu
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Yuan
Y
Wang
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Jing
J
Zhao
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Xiaoyan
X
Cheng
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Chen
C
Wang
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Mei
M
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D055785:Gene Knockdown Techniques; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D000091402:Prohibitins; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013440:Sulfides / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D014162:Transfection
D000970:Antineoplastic Agents; D001152:Arsenicals; C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D013440:Sulfides; C045816:arsenic trisulfide