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

Subin Thomas, John Paul, Akhila Shrungeswara, Subhankar Biswas, Aarti Shah, Chandrashekar Subraya, Yogendra Nayak

Research output: Contribution to journalArticle

Abstract

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 determined. Results: 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 extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.

Original languageEnglish
Pages (from-to)272-282
Number of pages11
JournalAsian Pacific Journal of Tropical Medicine
Volume12
Issue number6
DOIs
Publication statusPublished - 01-06-2019

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Annona
Diethylnitrosamine
Liver Neoplasms
Fruit
Chloroform
Liver
Inhibitory Concentration 50
Cell Movement
Cell Cycle
Apoptosis
Curcumin
Liver Function Tests
Hep G2 Cells
Hematologic Tests
Drinking Water
Wistar Rats
Hepatocellular Carcinoma
Oxidative Stress
Cell Count
Antioxidants

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Thomas, Subin ; Paul, John ; Shrungeswara, Akhila ; Biswas, Subhankar ; Shah, Aarti ; Subraya, Chandrashekar ; Nayak, Yogendra. / Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats. In: Asian Pacific Journal of Tropical Medicine. 2019 ; Vol. 12, No. 6. pp. 272-282.
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abstract = "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 determined. Results: 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 extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.",
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Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats. / Thomas, Subin; Paul, John; Shrungeswara, Akhila; Biswas, Subhankar; Shah, Aarti; Subraya, Chandrashekar; Nayak, Yogendra.

In: Asian Pacific Journal of Tropical Medicine, Vol. 12, No. 6, 01.06.2019, p. 272-282.

Research output: Contribution to journalArticle

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T1 - Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats

AU - Thomas, Subin

AU - Paul, John

AU - Shrungeswara, Akhila

AU - Biswas, Subhankar

AU - Shah, Aarti

AU - Subraya, Chandrashekar

AU - Nayak, Yogendra

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AB - 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 determined. Results: 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 extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.

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