This study establishes that betel nut induces dyslipidemia through its alkaloid, arecoline by inhibition of AMPK (Thr-172) and activation of ACC (Ser-79) and highlights the therapeutic potential of metformin for treatment of betel-nut induced carcinogenesis, indicating the repurposing of the old drug in a new avenue.
Besides, immunohistochemical analysis and qRT-PCR showed that the expression of fatty-acid synthase and acetyl-CoA carboxylase 1 were increased in the tongue and liver tissues of 4NQO-treated mice infected with <i>P. gingivalis</i>.These results showed that <i>P. gingivalis</i> promoted oral carcinogenesis and aggravated disturbance of fatty acid metabolism, indicating a close association among <i>P. gingivalis</i>, lipid metabolic and oral carcinogenesis.
FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics.
This study shows that lipogenesis is dispensable for liver tumorigenesis in mice treated with DEN, and identifies an important role for ACC enzymes in redox regulation and cell survival.
There is no clear role established for XAGE-1b, which is a member of the cancer testis antigen family in tumorigenesis and the metastasis process of ACC.