Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo

被引:156
作者
Adhami, Vaqar Mustafa [1 ]
Malik, Arshi [1 ]
Zaman, Najia [1 ]
Sarfaraz, Sami [1 ]
Siddiqui, Imtiaz Ahmad [1 ]
Syed, Deeba Nadeem [1 ]
Afaq, Farrukh [1 ]
Pasha, Farrukh Sierre [1 ]
Saleem, Mohammad [1 ]
Mukhtar, Hasan [1 ]
机构
[1] Univ Wisconsin, Dept Dermatol, Med Sci Ctr, Madison, WI 53706 USA
关键词
D O I
10.1158/1078-0432.CCR-06-2269
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Cyclooxygenase-2 (COX-2) inhibitors hold promise for cancer chemoprevention; however, recent toxicity concerns suggest that new strategies are needed. One approach to overcome this limitation is to use lower doses of COX-2 inhibitors in combination with other established agents with complementary mechanisms. In this study, the effect of (-) epigallocateo-catechin-3-gallate (EGCG), a promising chemopreventive agent from green tea, was tested alone and in combination with specific COX-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo. Experimental Design: Human prostate cancer cells LNCaP, PC-3, and CWR22R nu 1 were treated with EGCG and NS398 alone and in combination, and their effect on growth and apoptosis was evaluated. In vivo, athymic nude mice implanted with androgen-sensitive CWR22R nu 1 cells were given green tea polyphenols (0.1% in drinking water) and celecoxib (5 mg/kg, i.p., daily, 5 days per week), alone and in combination, and their effect on tumor growth was evaluated. Results: Combination of EGCG (10-40 mu mol/L) and NS-398 (10 mu mol/L) resulted in enhanced (a) cell growth inhibition; (b) apoptosis induction; (c) expression of Bax, pro-caspase-6, and pro-caspase-9, and poly(ADP)ribose polymerase cleavage; (d) inhibition of peroxisome proliferator activated receptor gamma; and (e) inhibition of nuclear factor-kappa B compared with the additive effects of the two agents alone, suggesting a possible synergism. In vivo, combination treatment with green tea polyphenols and celecoxib resulted in enhanced (a) tumor growth inhibition, (b) lowering of prostate-specific antigen levels, (c) lowering of insulin-like growth factor-I levels, and (d) circulating levels of serum insulin-like growth factor binding protein-3 compared with results of single-agent treatment. Conclusions: These data suggest synergistic and/or additive effects of combinatorial chemopreventive agents and underscore the need for rational design of human clinical trials.
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页码:1611 / 1619
页数:9
相关论文
共 50 条
[1]   Oral consumption of green tea polyphenols inhibits insulin-like growth factor-i-induced signaling in an autochthonous mouse model of prostate cancer [J].
Adhami, VM ;
Siddiqui, IA ;
Ahmad, N ;
Gupta, S ;
Mukhtar, H .
CANCER RESEARCH, 2004, 64 (23) :8715-8722
[2]   Molecular targets for green tea in prostate cancer prevention [J].
Adhami, VM ;
Ahmad, N ;
Mukhtar, H .
JOURNAL OF NUTRITION, 2003, 133 (07) :2417S-2424S
[3]   Rescuing COX-2 inhibitors from the waste bin [J].
Albini, A ;
Noonan, DM .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2005, 97 (11) :859-860
[4]   Cyclooxygenase inhibition in cancer prevention and treatment [J].
Anderson, WF ;
Umar, A ;
Hawk, ET .
EXPERT OPINION ON PHARMACOTHERAPY, 2003, 4 (12) :2193-2204
[5]   Molecular evidence for increased antitumor activity of gemcitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer [J].
Banerjee, S ;
Zhang, YX ;
Ali, S ;
Bhuiyan, M ;
Wang, ZW ;
Chiao, PJ ;
Philip, PA ;
Abbruzzese, J ;
Sarkar, FH .
CANCER RESEARCH, 2005, 65 (19) :9064-9072
[6]   Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: A preliminary report from a one-year proof-of-principle study [J].
Bettuzzi, S ;
Brausi, M ;
Rizzi, F ;
Castagnetti, G ;
Peracchia, G ;
Corti, A .
CANCER RESEARCH, 2006, 66 (02) :1234-1240
[7]   Activation of caspases-3,-6, and-9 during finasteride treatment of benign prostatic hyperplasia [J].
Bozec, A ;
Ruffion, A ;
Decaussin, M ;
Andre, J ;
Devonec, M ;
Benahmed, M ;
Mauduit, C .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (01) :17-25
[8]  
Brophy James M, 2005, Expert Opin Drug Saf, V4, P1005, DOI 10.1517/14740338.4.6.1005
[9]   The chemopreventive action of catechins in the TRAMP mouse model of prostate carcinogenesis is accompanied by clusterin over-expression [J].
Caporali, A ;
Davalli, P ;
Astancolle, S ;
D'Arca, D ;
Brausi, M ;
Bettuzzi, S ;
Corti, A .
CARCINOGENESIS, 2004, 25 (11) :2217-2224
[10]   QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].
CHOU, TC ;
TALALAY, P .
ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55