Adenosine induces cell-cycle arrest and apoptosis in androgen-dependent and -independent prostate cancer cell lines, LNcap-FGC-10, DU-145, and PC3

被引:59
作者
Aghaei, Mahmoud [1 ]
Karami-Tehrani, Fatemeh [1 ]
Panjehpour, Mojtaba [2 ,3 ,4 ]
Salami, Siamak [5 ]
Fallahian, Faranak [1 ]
机构
[1] Tarbiat Modares Univ, Sch Med Sci, Dept Clin Biochem, Canc Res Lab, Tehran, Iran
[2] Isfahan Univ Med Sci, Sch Pharm, Dept Clin Biochem, Esfahan, Iran
[3] Isfahan Univ Med Sci, Isfahan Pharmaceut Sci Res Ctr, Esfahan, Iran
[4] Isfahan Univ Med Sci, Bioinformat Res Ctr, Esfahan, Iran
[5] Urmia Univ Med Sci, Sch Med Sci, Dept Biochem, Orumiyeh, Iran
关键词
prostate cancer; adenosine; apoptosis; NERVOUS-SYSTEM; EXTRACELLULAR ADENOSINE; MAMMALIAN-CELLS; CARCINOMA-CELLS; HEPG2; CELLS; HL-60; RECEPTOR; GROWTH; PROLIFERATION; ACTIVATION;
D O I
10.1002/pros.21438
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via intrinsic and extrinsic pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the DU-145, PC3, and LNcap-FGC10 human prostate cancer cells. METHODS. To observe cell viability and proliferation, MTT assay, cell counting, and BrdU assay were carried out in DU-145, PC3, and LNcap-FGC10 cells. Apoptosis was assessed with the analysis of cell cycle, Hoechst 33258 staining, propidium iodide and annexin-V staining, reactive oxygen species (ROS) formation, mitochondrial membrane potential (DCM) measurement, caspase-3 activity assay, Bcl-2 and Bax protein expression. Moreover, the expression of adenosine receptors and the effects of adenosine receptor (A(1), A(2a), and A(3)) antagonists were examined. RESULT. Adenosine significantly reduced cell proliferation in a dose-dependent manner in DU-145, PC3, and LNcap-FGC10 cell lines. Adenosine induced arrest in the cell-cycle progression in G0/G1 phase through Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by morphological changes and increased sub-G1 population. Furthermore, increase of ROS, loss of MMP, activation of caspase-3, and down-regulation of Bcl-2 expression was observed. A1, A2a, A2b, and A3 adenosine receptors mRNA are expressed in the cell lines. Moreover, adenosine-induced apoptosis was inhibited by MRS1220, A3 adenosine receptor antagonist. CONCLUSION. Our results suggest that adenosine induced apoptosis in prostate cancer cells via the mitochondrial pathway and is related to the adenosine receptors. These data might suggest that adenosine could be used as an agent for the treatment of prostate cancer. Prostate 72: 361-375, 2012. (C) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:361 / 375
页数:15
相关论文
共 73 条
[11]   ADENOSINE, AN ENDOGENOUS ANTIINFLAMMATORY AGENT [J].
CRONSTEIN, BN .
JOURNAL OF APPLIED PHYSIOLOGY, 1994, 76 (01) :5-13
[12]   Mechanisms of apoptosis induced by purine nucleosides in astrocytes [J].
Di Iorio, P ;
Kleywegt, S ;
Ciccarelli, R ;
Traversa, U ;
Andrew, CM ;
Crocker, CE ;
Werstiuk, ES ;
Rathbone, MP .
GLIA, 2002, 38 (03) :179-190
[13]   GONADOTROPIN HORMONE-RELEASING HORMONE ANALOGS - A NEW THERAPEUTIC APPROACH FOR PROSTATIC-CARCINOMA [J].
EISENBERGER, MA ;
ODWYER, PJ ;
FRIEDMAN, MA .
JOURNAL OF CLINICAL ONCOLOGY, 1986, 4 (03) :414-424
[14]   Adenosine-induced apoptosis in EL-4 thymoma cells is caspase-independent and mediated through a non-classical adenosine receptor [J].
El-Darahali, A ;
Fawcett, H ;
Mader, JS ;
Conrad, DM ;
Hoskin, DW .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2005, 79 (03) :249-258
[15]   P2-PURINERGIC RECEPTOR AGONISTS INHIBIT THE GROWTH OF ANDROGEN-INDEPENDENT PROSTATE CARCINOMA-CELLS [J].
FANG, WG ;
PIRNIA, F ;
BANG, YJ ;
MYERS, CE ;
TREPEL, JB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (01) :191-196
[16]   Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor [J].
Fishman, P ;
Bar-Yehuda, S ;
Ohana, G ;
Pathak, S ;
Wasserman, L ;
Barer, F ;
Multani, AS .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (11) :1452-1458
[17]   Adenosine, mast cells and asthma [J].
Forsythe, P ;
Ennis, M .
INFLAMMATION RESEARCH, 1999, 48 (06) :301-307
[18]   PURINOCEPTORS IN THE NERVOUS-SYSTEM [J].
FREDHOLM, BB .
PHARMACOLOGY & TOXICOLOGY, 1995, 76 (04) :228-239
[19]  
Fredholm BB, 2001, PHARMACOL REV, V53, P527
[20]  
Fredholm BB, 1997, INT REV NEUROBIOL, V40, P259