[show abstract][hide abstract] ABSTRACT: Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP) in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01). This combination also significantly regressed tumor volume and number (p<0.01). Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15) in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.
PLoS ONE 01/2011; 6(8):e23395. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The perception of chemoprevention lies still in its infancy. Intervention, to slow down, arrest or reverse the process of carcinogenesis, by the use of either natural or synthetic substances individually or in combination therapy has emerged as a promising and pragmatic medical approach to reduce cancer risk. Pentacyclic lupane-type triterpenes exemplified by lupeol [lup-20(29)-en-3b-ol], are principally found in common fruit plants such as olive, mango, fig, etc. Although, lupeol exhibits an array of biological activities like anti-inflammatory, anti-arthritic, anti-mutagenic and anti-malarial activity both in in vitro and in vivo systems yet, extensive exploration in regard to establish its role as chemopreventive compound is warranted. Interest in developing lupeol based potent anti-neoplastic agents, has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices. This review asserts on the chemopreventive prospects of lupeol and reveals potential chemoprevention drug targets, central to which are the cell cycle regulatory pathway genes and tries to explain the mechanism operating behind its action.
Cancer Letters 06/2008; 263(1):1-13. · 4.26 Impact Factor