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    • Keywords


      Amarogentin; liver carcinogenesis; epigenetics; LIMD1; P16; DNMT1

    • Abstract


      Amarogentin (active component of Chirata) was found to prevent CCl4/NDEA-induced liver carcinogenesis atmild dysplastic stage through modulation of cell cycle, apoptosis, self-renewal pathways. The cell cycleregulatory genes LIMD1, P16 and RBSP3 were found to be upregulated in restricted liver lesions. Tounderstand the mechanism of upregulation during restriction of cacinogenesis, the effect of amarogentin onepigenetic modification was evaluated in this study. It was also validated in vitro. Hypermethylation of LIMD1and P16 was seen in mouse hepatocellular carcinoma (30th week carcinogen control mice); however,hypomethylation of these genes was seen in amarogentin-treated liver. In the case of RBSP3, no such changewas seen. DNMT1 expression (mRNA/protein) was significantly increased in later stages of carcinogenesis,whereas its expression was comparable to normal liver in the case of amarogentin treatment. No significantchange in expression (mRNA/protein) of HDAC1/2 was observed irrespective of treatment. Amarogentintreatment upregulated the expression (mRNA/protein) of LIMD1, P16 and RBSP3 in the HepG2 cell line. Herealso treated cells showed LIMD1 and P16 hypomethylation with DNMT1 downregulation. Increased expressionof LIMD1, P16 and RBSP3 after treating cells with demethylating agent 5-aza-2-deoxycytidine indicatedepigenetic modulation by amarogentin treatment.

    • Author Affiliations



      1. Department Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700 026, India
      2. Department of Pathology, Saint Louis University, Saint Louis, USA
      3. Department of Chemistry, National Research Institute for Ayurvedic Drug Development, Kolkata, India
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