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Bergapten Inhibits Liver Carcinogenesis by Modulating LXR/PI3K/Akt and IDOL/LDLR Pathways

Bergapten Inhibits Liver Carcinogenesis by Modulating LXR/PI3K/Akt and IDOL/LDLR Pathways

Shakti Prasad Pattanayak, Pritha Bose, Priyashree Sunita, Mohd Usman Mohd Siddique, Antonio Lapenna

Biomed Pharmacother. 2018 Dec;108:297-308.

PMID: 30227322

Abstract:

Oxysterol receptors LXRs (α and β) are recently reported to be one of the novel and potential therapeutic targets in reducing cell proliferation and tumor growth in different system model. Activation of LXRs is correlated with modification of PI3K/Akt pathway. LXRs are also found to play a critical role in maintaining lipid homeostatais by regulating ABCA1, IDOL, SREBP1, LDLR and also certain lipogenic genes such as FASN and SCD1. In the present study a potential furanocoumarin, Bergapten (BeG) has been evaluated for its anticancer property on Hepatocellular Carcinoma (HCC) on LXR axis. The molecular docking analysis was carried out for BeG on LXR (α & β) using Maestro tool and compared with reference ligands. This was followed by in vitro (HepG2 cell lines) and in vivo (on NDEA induced HCC in Wistar albino rats) anticancer evaluation of BeG. The docking results revealed polar and hydrophobic interactions of BeG with LXR (α,β). The in vitro studies revealed the potential of BeG in lowering the accumulation of lipid droplets in HepG2 cells which was correlated with increase in LXR (α,β) protein expressions. Furthermore, the in vivo studies demonstrated the potential of BeG in ameliorating the cancer induced alterations in body weight, liver weight and significant restoration of the changes in mRNA and protein expressions of LXR(α,β), ABCA1, IDOL, SREBP1 and LDLR. BeG also modulated the expressions of PI3K, Akt and certain lipogenic genes like FASN and SCD1 and reduced the lipid droplets level in liver cancer cells. These results provide evidence and validates the critical role of BeG in maintaining the lipid homeostasis and justifies its anticancer potential against NDEA-induced HCC.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP484208-A	Bergapten		484-20-8	Price

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