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Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats

Asian Pacific Journal of Tropical Medicine 2019年第6期12卷 272-282页

作者： Subin Varghese Thomas John Paul Akhila Hosur Shrungeswara Subhankar Biswas Aarti Abhishek Shah Chandrashekar Kodangala Subraya yogendra nayak Department of Pharmacology Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia Department of Pharmacy Practice Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia Department of Pharmacognosy Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia

Objective: To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine(DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were ***: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity (IC50=(53.7±4.3) μg/mL)The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit ***: The Annona muricata fruit extract has

关键词： HepG2-cells Apoptosis Liver cancer Acetogenins Rat liver cancer Scratch wound assay

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