Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 1
- DOI:
- No doi available
- Key Word:
- nuclear matrix;arsenic trioxide;PML protein;apoptosis;HepG2 cell line
Abstract： Objective To investigate arsenic trioxide (As2O3)-induced apoptosis and the effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Methods HepG2 cells were cultured in MEM medium and treated with 0.5, 2, 5 and 10 μmol/L As2O3 for either 24 h or 96 h at each concentration. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladders were used to detect apoptosis. Confocal microscopy and Western blotting were used to observe the expression of PML. Results The growth rates of HepG2 cells were slower in the As2O3 treated than the untreated control group. DNA ladder and TUNEL positive apoptotic cells could be detected in As2O3 treated groups. The expression of PML decreased in HepG2 cells with 2 μmol/L As2O3 treatment. Confocal images demonstrated that the expression of PML protein in HepG2 cell nuclei decreased after treatment with 2 μmol/L As2O3, and micropunctates characteristic of PML protein in HepG2 cell nuclei disappeared after treatment with 5 μmol/L As2O3.Conclusions Our results show that arsenic trioxide can significantly inhibit the growth of HepG2 cells in vitro. As2O3 induces apoptosis in HepG2 tumor cells in a time and concentration dependent manner. As2O3 may degrade the PML protein in HepG2 cell nuclei. The decreased expression of PML in As2O3 treated tumor cells is most likely to be caused by apoptosis. Nuclear matrix associated protein PML could be the target of As2O3 therapy.
- [1]Quignon F.,Degos L.,Dethe H.,etc.Arsenic-Induced Pml Targeting onto Nuclear Bodies - Implications for the Treatment of Acute Promyelocytic Leukemia[J].1997,94(8).
- [2]Y H, Du,P C, Ho.Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines.[J].2001,47(6).
- [3]X H, Zhu,Y L, Shen,Y K, Jing,etc.Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations.[J].1999,91.
- [4]Zhang TD,Wang ZY,Chen Z,etc.Arsenic trioxide, a therapeutic agent for APL.[J].2001,20(49).
- [5]L, Liu,S, Qin,H, Chen,etc.[An experimental study on arsenic trioxide-selectively induced human hepatocarcinoma cell lines apoptosis and its related genes].[J].2000,8.
- [6]P, Rousselot,S, Labaume,J P, Marolleau,etc.Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients.[J].1999,59.
- [7]I, Ora,L, Bondesson,C, J?nsson,etc.Arsenic trioxide inhibits neuroblastoma growth in vivo and promotes apoptotic cell death in vitro.[J].2000,277(1).
- [8]E G, Fey,S, Penman.Nuclear matrix proteins reflect cell type of origin in cultured human cells.[J].1988,85.
- [9]L, Shen,T X, Chen,Y P, Wang,etc.As2O3 induces apoptosis of the human B lymphoma cell line MBC-1.[J].1900,14.
- [10]K J, Pienta,A W, Partin,D S, Coffey.Cancer as a disease of DNA organization and dynamic cell structure.[J].1989,49.
- [11]Murgo AJ.Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies.[J].2001,6(Suppl.2).
- [12]J.Y.H Chan,W Chin,C.-T Liew,etc.Altered expression of the growth and transformation suppressor PML gene in human hepatocellular carcinomas and in hepatitis tissues[J].1998,34(7).
- [13]C, Andre,M C, Guillemin,J, Zhu,etc.The PML and PML/RARalpha domains: from autoimmunity to molecular oncology and from retinoic acid to arsenic.[J].1996,229.
- [14]Ruthardt M,Hoelzer D,Jensen K,etc.PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.[J].1999,19(7).
- [15]Khan MM,Nomura T,Kim H,etc.Role of PML and PML-RARalpha in Mad-mediated transcriptional repression.[J].2001,7(6).
- [16]H, Chen,S, Qin,Q, Pan.[Antitumor effect of arsenic trioxide on mice experimental liver cancer].[J].2000,8(1).
- [17]Z H, Wang,H F, Yam,P C, Or,etc.Effects of all-trans-retinoic acid on human esophageal carcinoma cells and their nuclear matrices.[J].1900,19.
- [18]S, Meyers,S W, Hiebert.Alterations in subnuclear trafficking of nuclear regulatory factors in acute leukemia.[J].2000,Suppl 35.
- [19]He LZ,Peruzzi D,Pandolfi PP,etc.Role of promyelocytic leukemia (PML) protein in tumor suppression.[J].2001,193(4).
- [20]Kim BK,Park WH,Lee YY,etc.Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells.[J].2001,18(2).
- [21]Waxman S,Anderson KC.History of the development of arsenic derivatives in cancer therapy.[J].2001,6(Suppl.2).
- [22]G Q, Chen,J, Zhu,X G, Shi,etc.In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins.[J].1996,88.
- [23]T.-C Zhang,E.-H Cao,J.-F Li,etc.Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide[J].1999,35(8).