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Abstract Title:

Demethylating and anti-hepatocarcinogenic potential of hesperidin, a natural polyphenol of Citrus juices.

Abstract Source:

Mol Carcinog. 2017 Jan 27. Epub 2017 Jan 27. PMID: 28130850

Abstract Author(s):

Zahira Fernández-Bedmar, Jaouad Anter, Angeles Alonso-Moraga, Juana Martín de Las Mulas, Yolanda Millán-Ruiz, Silvia Guil-Luna

Article Affiliation:

Zahira Fernández-Bedmar

Abstract:

Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy. The purpose of the present study was to evaluate the methylation patterns induced by hesperidin in HL60 cell line as an in vitro model in order to analyze its chemopreventive effects in epigenetic cancer therapies. A parallel in vivo pilot experience using a rat diethyl nitrosamine hepatocarcinogenesis-induced model was carried out to validate the therapeutic efficacy of this orange flavonol. Results showed that: (i) Hesperidin is cytotoxic in a dose-dependent manner and the IC50 was 12.5 mM; (ii) Hesperidin exerts a significant hypomethylating effect on the LINE-1 sequence (up to 47% hypomethylation at 12.5 mM) and on the ALU-M2 repetitive sequences (up to 32% at 6 mM) in HL60 tumor cells. (iii) Hesperidin does not affect the rat body and liver weight and it is able to reducethe diethyl nitrosamine-induced nodules at 1000, 500 and 250 ppm. In conclusion, hesperidin could be proposed as a candidate molecule in chemoprevention in epigenetic therapy purposes. This article is protected by copyright. All rights reserved.

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