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

Vaqar Mustafa Adhami, Arshi Malik, Najia Zaman, Sami Sarfaraz, Imtiaz Ahmad Siddiqui, Deeba Nadeem Syed, Farrukh Afaq, Farrukh Sierre Pasha, Mohammad Saleem, Hasan Mukhtar

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

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 (-)epigallocate-ocatechin-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 CWR22Rν1 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 CWR22Rν1 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 μmol/L) and NS-398 (10 μmol/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 γ; and (e) inhibition of nuclear factor-κB 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.

Original languageEnglish (US)
Pages (from-to)1611-1619
Number of pages9
JournalClinical Cancer Research
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this