Polymeric black tea polyphenols inhibit 1,2-dimethylhydrazine induced colorectal carcinogenesis by inhibiting cell proliferation via Wnt/beta-catenin pathway.
Tea polyphenols like epigallocatechin gallate and theaflavins are established chemopreventive agents for colorectal carcinogenesis. However, studies on evaluating similar chemopreventive properties of thearubigins or polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited. Hence, in the present study we aim to investigate chemopreventive effects along with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Sprague-Dawley rats as experimental model. The present study suggests that PBPs, like other tea polyphenols, also inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and multiplicity. This study also shows that although the pretreatment with PBP extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did not show any additional chemopreventive effects when compared to treatments with PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit colorectal carcinogenesis by decreasing DMH-induced cell proliferation via Wnt/beta-catenin pathway. Treatments with PBP extract showed decreased levels of COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by regulating beta-catenin by maintaining expression of APC and decreasing inactivation of GSK3beta. DMH-induced activation of MAP kinases such as ERK and JNK was also found to be inhibited by treatments with PBP extract. In conclusion, the protective effects of PBP extract could be attributed to inhibition of DMH-induced cellular proliferation probably through beta-catenin regulation.
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai-410 210, India.
Rachana
R
Patel
Arvind
A
Ingle
Girish B
GB
Maru
D019813:1,2-Dimethylhydrazine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D005419:Flavonoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013662:Tea / Q000737:chemistry*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D002273:Carcinogens; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D051153:Wnt Proteins; D051176:beta Catenin; D019813:1,2-Dimethylhydrazine