resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated mapks and p53白藜芦醇和红茶多酚组合协同抑制小鼠皮肤肿瘤的生长激活mapks和p53的抑制.pdfVIP

Resveratrol and Black Tea Polyphenol Combination Synergistically Suppress Mouse Skin Tumors Growth by Inhibition of Activated MAPKs and p53 Jasmine George, Madhulika Singh, Amit Kumar Srivastava, Kulpreet Bhui, Preeti Roy, Pranav Kumar Chaturvedi, Yogeshwer Shukla* Proteomics Laboratory, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Uttar Pradesh, India 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 additio