Ursolic acid, a naturally occurring triterpenoid, demonstrates anticancer activity on human prostate cancer cells

被引:90
作者
Kassi, E.
Papoutsi, Z.
Pratsinis, H.
Aligiannis, N.
Manoussakis, M.
Moutsatsou, P.
机构
[1] Univ Athens, Sch Med, Dept Biol Chem, Athens 11527, Greece
[2] NCSR Demokritos, Inst Biol, Lab Cell Proliferat & Ageing, GR-15310 Athens, Greece
[3] Univ Athens, Dept Pharm, Lab Pharmacognosy, GR-15771 Athens, Greece
[4] Univ Athens, Sch Med, Lab Pathophysiol, Athens 11527, Greece
关键词
LNCaP cells; dexamethasone; RU486; ursolic acid; prostate cancer;
D O I
10.1007/s00432-007-0193-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Glucocorticoids are widely used as adjuvant therapy in hormonal refractory prostate cancer; their therapeutic role, however, remains unclear. Ursolic acid, a natural triterpene, structurally similar to dexamethasone, exhibits antitumor effects in various cell types. Our main objective was to investigate the effects of ursolic acid on cell viability, apoptosis and bcl-2 protein, in human hormone refractory and androgen-sensitive prostate cancer cells. Methods The ursolic acid-induced changes in cell viability, apoptosis and bcl-2 protein were examined in human hormone refractory prostate cancer PC-3 cells and androgen-sensitive LNCaP cells, by MTT assay, flow cytometry and western blot analysis, respectively. Results Ursolic acid inhibited significantly the cell viability and induced apoptosis in PC-3 cells at 55 mu M and in LNCaP cells at 45 mu M associated with a downregulation of bcl-2 protein. Conclusions The antiproliferative and apoptotic effects of ursolic acid in PC-3 and LNCaP cells implicate its potential therapeutic use for the treatment of hormone refractory and androgen-sensitive prostate cancer. The downregulation of bcl-2 may be one of the molecular mechanisms via which it induces apoptosis in PC-3 and LNCaP cells.
引用
收藏
页码:493 / 500
页数:8
相关论文
共 35 条
[1]   Apoptosis in prostate carcinogenesis - A growth regulator and a therapeutic target [J].
Bruckheimer, EM ;
Kyprianou, N .
CELL AND TISSUE RESEARCH, 2000, 301 (01) :153-162
[2]  
Buchanan G, 2001, CLIN CANCER RES, V7, P1273
[3]   Synergistic and antagonistic combinations of drugs in human prostate cancer cell lines in vitro [J].
Budman, DR ;
Calabro, A ;
Kreis, W .
ANTI-CANCER DRUGS, 2002, 13 (10) :1011-1016
[4]  
Carollo M, 1998, ONCOL RES, V10, P245
[5]   Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells [J].
Cha, HJ ;
Park, MT ;
Chung, HY ;
Kim, ND ;
Sato, H ;
Seiki, M ;
Kim, KW .
ONCOGENE, 1998, 16 (06) :771-778
[6]  
Chodak Gerald, 2006, Rev Urol, V8 Suppl 2, pS3
[7]  
Choi YH, 2000, INT J ONCOL, V17, P565
[8]   Both androgen receptor and glucocorticoid receptor are able to induce prostate-specific antigen expression, but differ in their growth-stimulating properties of LNCaP cells [J].
Cleutjens, CBJM ;
Steketee, K ;
VanEekelen, CCEM ;
VanderKorput, JAGM ;
Brinkmann, AO ;
Trapman, J .
ENDOCRINOLOGY, 1997, 138 (12) :5293-5300
[9]   Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter [J].
Cleutjens, KBJM ;
vanEekelen, CCEM ;
vanderKorput, HAGM ;
Brinkmann, AO ;
Trapman, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (11) :6379-6388
[10]   RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].
DENIZOT, F ;
LANG, R .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277