Prevention of inorganic arsenic induced squamous cell carcinoma of the skin in Swiss albino mice by black tea through epigenetic modulation

Consumption of inorganic Arsenic (iAs) above the safe level may lead to many diseases including cancers of skin. It is known that carcinogenicity of iAs is mediated through generation of excessive reactive oxygen species and polyphenols present in black tea extract (BTE) ameliorate the deleterious effect. Epigenetics also plays vital roles in carcinogenesis. The aim of this paper is to study the influence of iAs on epigenetics and the modulatory effect of BTE. Male Swiss albino mice were divided into three groups, (i) control, (ii) iAs-administered and (iii) iAs + BTE administered. Group (ii) developed invasive squamous cell carcinoma (SCC) of the skin after 330 days, while only hyperplasic and dysplastic changes were observed in group (iii). Expression levels of histone methylation, acetylation marks and several histone methylases, demethylases and acetylases due to iAs were studied; most aberrant expression levels due to iAs were modulated by BTE. JARID1B, a histone demethylase implicated as one of the markers in SCC and a therapeutic target gets upregulated by iAs, but is not influenced by BTE. However, SCC is prevented by BTE. Upregulation of JARID1B by iAs represses H3K4me3; BTE upregulates H3K4me3 without influencing JARID1B expression level. It is known that theaflavin compounds in BTE are transported to the nucleus and interact with histone proteins. in-silico findings in this paper hint that theaflavin compounds present in BTE are very good inhibitors of JARID1B and BTE inhibits its demethylating activity. BTE reverses the epigenetic alterations caused by iAs, thus aids in prevention of SCC.