title: Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice.
abstract: The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30thweeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30thweek. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF.
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India. Electronic address: subhayansur18@gmail.com.
authors.forename: Subhayan
authors.initials: S
authors.lastname: Sur
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India.
authors.forename: Debolina
authors.initials: D
authors.lastname: Pal
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Roy
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India.
authors.forename: Atish
authors.initials: A
authors.lastname: Barua
authors.affiliation: North Bengal Medical College and Hospital, West Bengal, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India.
authors.forename: Prosenjit
authors.initials: P
authors.lastname: Saha
authors.affiliation: Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India. Electronic address: ckpanda.cnci@gmail.com.
authors.forename: Chinmay Kumar
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology*; D001835:Body Weight; D063646:Carcinogenesis / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004052:Diethylnitrosamine / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D059808:Polyphenols / Q000494:pharmacology; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D044946:Biflavonoids; D053823:Hedgehog Proteins; D059808:Polyphenols; D051153:Wnt Proteins; D051176:beta Catenin; C056068:theaflavin; D004052:Diethylnitrosamine; D002392:Catechin; C045651:epigallocatechin gallate
keywords: EGCG; Gli1; Liver carcinogenesis; TF; Tongue carcinogenesis; β-catenin