Antiproliferative and Chemopreventive effect of Annona muricata Linn. on Ehrlich ascites carcinoma and Benzo[a]pyrene induced lung carcinoma

Abstract

Annona muricata Linn. also called “Soursop” or “Sharp Sharp” is traditionally used in treatment of cancer. There are many claims that Annona muricata L. can kill cancer cells, since its leaves, seeds and fruits contain active compound called annonaceous acetogenins. This research was aimed to evaluate the antiproliferative and chemopreventive effect of Annona muricata L. leaf extract against Ehrlich ascites carcinoma and benzo[a]pyrene induced lung carcinoma. In Ehrlich ascites carcinoma model, the tumor bearing mice treated with methanol extract of Annona muricata leaves 200 mg/kg and 400 mg/kg once daily orally started 24 h after inoculation significantly reduced the viable cell count. The dose level of 400 mg/kg showed a significant increase in non-viable count with a significant decrease in body weight of animals compared to EAC control animals. The haematological parameters were reverted to more or less normal levels in animals treated with extract 400 mg/kg. In benzo[a]pyrene induced lung cancer model, treatment with extract started 1 week before benzo[a]pyrene induction and continued once daily for 16 weeks, effectively suppressed lung cancer. There was a significant increase in weight gain during experimental period with a significant decrease in relative lung weight and serum cancer marker - carcinoembryonic antigen at the end of experimental period. Gross morphology of lung also appeared near normal to lung of normal animals. Moreover, with reference to lipid peroxidation and antioxidant system, Annona muricata leaf extract decreased the extent of lipid peroxidation with concomitant increase in activities of superoxide dismutase, catalase and reduced glutathione compared to lung cancer bearing untreated animals. It was observed that extract 400 mg/kg showed a significant protection against benzo[a]pyrene induced carcinogenesis. Histological examination of lung tissue too correlated with morphological and biochemical observations. Our data suggest that, the potential anti-proliferative and chemopreventive action of Annona muricata leaves might be due to cytotoxic mechanism against cancer cells in the pathway of apoptosis and inhibition of cell cycle. Furthermore, our in-vitro investigation on extract showed a potent free radical scavenging activity. An additional antioxidant property of Annona muricata leaves might be responsible for chemoprevention by stabilizing all the components of antioxidant defense which were disturbed during benzo[a]pyrene induced oxidative damage.

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Acknowledgments

The authors are thankful to the management of JKK Nataraja College of Pharmacy, Komarapalayam, Tamil Nadu, INDIA for providing necessary facilities to carry out the research work.

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Correspondence to Venugopalan Rajesh.

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Ethical clearance (for handling of animals and the procedures used in study) was obtained from the Institutional Animal Ethical Committee Proposal number- 02MP16JUN14 (887/ac/05/CPCSEA) before performing the study on animals.

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Rajesh, V., Baby Kala, M. Antiproliferative and Chemopreventive effect of Annona muricata Linn. on Ehrlich ascites carcinoma and Benzo[a]pyrene induced lung carcinoma. Orient Pharm Exp Med 15, 239–256 (2015). https://doi.org/10.1007/s13596-015-0199-1

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Keywords

  • Annona muricata L, leaves
  • Ehrlich ascites carcinoma
  • Benzo[a]pyrene induced lung cancer
  • Antioxidant activity