Hypomethylation of LIMD1 and P16 by downregulation of DNMT1 results in restriction of liver carcinogenesis by amarogentin treatment
Amarogentin (active component of Chirata ) was found to prevent CCl4/NDEA-induced liver carcinogenesis at mild dysplastic stage through modulation of cell cycle, apoptosis, self-renewal pathways. The cell cycle regulatory genes LIMD1, P16 and RBSP3 were found to be upregulated in restricted liver le...
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Published in | Journal of biosciences Vol. 46; no. 3 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New Delhi
Springer India
01.09.2021
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Amarogentin (active component of
Chirata
) was found to prevent CCl4/NDEA-induced liver carcinogenesis at mild dysplastic stage through modulation of cell cycle, apoptosis, self-renewal pathways. The cell cycle regulatory genes
LIMD1, P16
and
RBSP3
were found to be upregulated in restricted liver lesions. To understand the mechanism of upregulation during restriction of cacinogenesis, the effect of amarogentin on epigenetic modification was evaluated in this study. It was also validated
in vitro
. Hypermethylation of
LIMD1
and
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 change was 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 significant change in expression (mRNA/protein) of
HDAC1
/2 was observed irrespective of treatment. Amarogentin treatment upregulated the expression (mRNA/protein) of
LIMD1, P16
and
RBSP3
in the HepG2 cell line. Here also treated cells showed
LIMD1
and
P16
hypomethylation with
DNMT1
downregulation. Increased expression of
LIMD1
,
P16
and
RBSP3
after treating cells with demethylating agent 5-aza-2-deoxycytidine indicated epigenetic modulation by amarogentin treatment. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0250-5991 0973-7138 |
DOI: | 10.1007/s12038-021-00176-0 |