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Abstract Title:

Could PCSK9 be a new therapeutic target of Eugenol? In vitro and in silico evaluation of hypothesis.

Abstract Source:

Med Hypotheses. 2019 Nov 27 ;136:109513. Epub 2019 Nov 27. PMID: 31812013

Abstract Author(s):

Saadiya Zia, Sidra Batool, Ramla Shahid

Article Affiliation:

Saadiya Zia

Abstract:

PCSK9 (Proprotein convertase Subtilisin/Kexin Type 9), an important regulator of lipid metabolism, has been shown to play a role in hepatocellular carcinoma by promoting metastasis. PCSK9 interferes with LDL metabolism and causes dyslipidemias in hematological malignancies particularly acute lymphoblastic leukemia. Nutraceuticals like berberine, curcumin and polydatin have been found effective in modulating PCSK9 expression by lowering LDL levels. Eugenol, a nutraceutical has shown a promising role in cancer due to its antioxidant and antihypercholesterolemic effects. In the present study, PCSK9 expression was measured in acute lymphoblastic leukemia (ALL) patients and was found to be significantly induced. Based on the results of expression analysis, a plausible hypothesis was made. Eugenol being an antioxidant will prevent oxidation of LDL. In the absence of ox-LDL, LOX1 scavenger receptor, which regulates PCSK9 expression, will not be activated. As the circulating LDL is reduced, it will no longer be able to support leukemia cell growth. The hypothesis was validated by an in silico and in vitro study. Molecular docking revealed hydrophobic interactions between ligand eugenol and macromolecules PCSK9 and LOX1. Expression of both PCSK9 and LOX1 were significantly reduced by eugenol in Jurkat cells. To conclude, PCSK9 could therapeutically be targeted by eugenol in leukemia cells.

Study Type : In Vitro Study

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