Advertisement

Oriental Pharmacy and Experimental Medicine

, Volume 15, Issue 4, pp 239–256 | Cite as

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

  • Venugopalan RajeshEmail author
  • Maathan Baby Kala
Research Article

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.

Keywords

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

Notes

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.

Compliance with Ethical Standards

Ethical Statement

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.

Conflict of Interest

The authors declare that there are no conflicts of interest.

References

  1. Antoun MD, Gerena L, Milhus WK (1993) Screening of the flora of Puerto rico for potential antimalarial bioactives. Int J Pharmacogn 31:255–258CrossRefGoogle Scholar
  2. Arkcoll D (1990) New crops from Brazil. In: Janick J, Simon JE (eds) Advances in new crops. Timber press, Portland, pp 367–371Google Scholar
  3. Banerjee S, Das S (2004) Chemopreventive efficacy of black tea on benzo[a]pyrene induced lung carcinogenesis. Int J Cancer Prev 1:129–136Google Scholar
  4. Baskar R, Rajeswari V, Kumar TS (2007) In-vitro antioxidant studies in leaves of Annona species. Indian J Exp Biol 45(5):480–485PubMedGoogle Scholar
  5. Bebe FN, Panemangalore M (2003) Exposure to low doses of endosulfan and chlorpyrifos modifies endogenous antioxidants in tissues of rats. J Environ Sci Health B 38(3):349–363CrossRefPubMedGoogle Scholar
  6. Bhattracharya S, Chatterjee M (1998) Protective role of Trianthema portulacastrum against diethylnitrosamine- induced experimental hepatocarcinogenesis. Cancer Lett 129(1):7–13CrossRefGoogle Scholar
  7. Bishop JM (1991) Molecular themes in oncogenesis. Cell 64(2):235–248CrossRefPubMedGoogle Scholar
  8. Blois MS (1958) Antioxidant determinations by the use of a stable free radical. Nature 181:1199–1200CrossRefGoogle Scholar
  9. Chang C, Yang M, Wen H, Chen J (2002) Estimation of total flavonoids content in propolis by two complementary colorimetric methods. J Food Drug Anal 10(3):178–182Google Scholar
  10. Chemoprevention working group (1999) Prevention of cancer in the next millennium: report of the chemoprevention working group to the American Association of Cancer Research. Cancer Res 59(19):4743–4758Google Scholar
  11. Cragg GM, Newman DJ (2000) Antineoplastic agents from natural sources: achievements and future directions. Expert Opin Investig Drugs 9(12):2783–2797CrossRefPubMedGoogle Scholar
  12. Dargel R (1992) Lipid peroxidation - a common pathogenetic mechanism? Exp Toxicol Pathol 44(4):169–181CrossRefPubMedGoogle Scholar
  13. De Feo V (1992) Medicinal and magical plants in the Northern Peruvian Andes. Fitoterapia 63(5):417–440Google Scholar
  14. De S. Luna J, De Carvalho JM, De Lima MR, Bieber LW, Bento Ede S, Franck X, Santana AE (2006) Acetogenins in Annona muricata L. (Annonaceae) leaves are potent molluscicides. Nat Prod Res 20(3):253–257CrossRefGoogle Scholar
  15. De Sousa OV, Vieira GD, de Jesus RG, de Pinho YCH, Alves SV (2010) Antinociceptive and anti-inflammatory activities of the ethanol extract of annona muricata L. Leaves in animal models. Int J Mol Sci 11(5):2067–2078PubMedCentralCrossRefPubMedGoogle Scholar
  16. Duh PD, Yen GH (1997) Antioxidative activity of three herbal water extracts. Food Chem 60(40):639–645CrossRefGoogle Scholar
  17. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Lett 223(2):181–190CrossRefPubMedGoogle Scholar
  18. Eggadi V, Gundamedi S, Sheshagiri SBB, Revoori SK, Jupally VR, Kulandaivelu U (2014) Evaluation of anticancer activity of Annona muricata in 1, 2-Dimethyl hydrazine induced colon cancer. World Appl Sci J 32(3):444–450Google Scholar
  19. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC (1998) Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 280(18):1569–1575CrossRefPubMedGoogle Scholar
  20. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70–77CrossRefPubMedGoogle Scholar
  21. Ezirim AU, OkochiVI JAB, Adebeshi OA, Ogunnowos OOB (2013) Induction of apoptosis in myelogenous leukemic K562 cells by ethanolic leaf extract of Annona muricata. Glob J Res Med Plants Indigen Med 2(3):142–151Google Scholar
  22. Farombi EO, Olowg BI, Emerole GO (2000) Effect of three structurally related antimalarial drugs on liver microsomal components and lipid peroxidation in rats. Comp Biochem Physiol C Toxicol Pharmacol 126(3):217–224PubMedGoogle Scholar
  23. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and (15 N) nitrate in biological fluids. Anal Biochem 126(1):131–138CrossRefPubMedGoogle Scholar
  24. Hamizah S, Roslida AH, Fezah O, Tan KL, Tor YS, Tan CI (2012) Chemopreventive potential of Annona muricata L. leaves on chemically-induced skin papillomagenesis in mice. Asian Pac J Cancer Prev 13(6):2533–2539CrossRefPubMedGoogle Scholar
  25. Hecht SS, Upadhyaya P, Wang M, Bliss RL, Mclntee EJ, Kenney PM (2002) Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbomyl)-L-cysteine and myo-inositol individually and in combination. Carcinogenesis 23(9):1455–1461CrossRefPubMedGoogle Scholar
  26. Heinrich M, Kuhnt M, Wright CW, Rimpler H, Phillipson JD, Schandelmaier A, Warhurst DC (1992) Parasitological and microbiological evaluation of mixed Indian medicinal plants (Mexico). J Ethnopharmacol 36:81–85CrossRefPubMedGoogle Scholar
  27. Hepsibha BT, Sathiya S, Babu CS, Premalakshmi V, Sekar T (2010) In vitro studies of antioxidant and free radical scavenging activities of Azima tetracantha Lam. leaf extract. Indian J Sci Technol 3:571–577Google Scholar
  28. Jagadeeswaran R, Thirunavukkarasu C, Nalini R, Gunasekaran S, Sakthisekaran D (2000) In-vitro studies on the selective cytotoxic effect of crocetin and quercetin. Fitotherapia 71(4):395–399CrossRefGoogle Scholar
  29. Jahan MS, Vani G, Shyamaladevi CS (2011) Anti-carcinogenic effect of Solanum trilobatum in diethylnitrosamine induced and Phenobarbital promoted hepatocarcinogenesis in rats. Asian J Biochem 6(1):74–81Google Scholar
  30. Joyce Nirmala M, Samundeeswari A, Deepa Sankar P (2011) Natural plant resources in anti-cancer therapy-A review. Res Plant Biol 1(3):1–14Google Scholar
  31. Kakkar P, Das B, Viswanath PN (1984) A Modified spectrophotometer assay of superoxide dismutase (SOD). Indian J Biochem Biophys 21(2):130–132PubMedGoogle Scholar
  32. Karmakar I, Dolai N, Saha P, Sarkar N, Bala A, Haldar PK (2011) Scavenging activity of Curcuma caesia rhizome against reactive oxygen and nitrogen species. Orient Pharm Exp Med 11(4):221–228CrossRefGoogle Scholar
  33. Kim J, Park EJ (2002) Cytotoxic anticancer candidates from natural resources. Curr Med Anticancer Agents 2(4):485–537CrossRefGoogle Scholar
  34. Kim HS, Kwack SL, Lee BM (2000a) Lipid peroxidation and antioxidant enzymes in the blood of rats treated with benzo[a]pyrene. Chem Biol Interact 127(2):139–150CrossRefPubMedGoogle Scholar
  35. Kim KS, Kwack SJ, Lee BM (2000b) Lipid peroxidation, antioxidant enzymes and benzo[a]pyrene-quinones in the blood of rats treated with benzo[a]pyrene. Chem Biol Interact 127(2):139–150CrossRefPubMedGoogle Scholar
  36. Kokate CK (1994) Practical Pharmacognosy. 4thed, Vallabah Prakashan, New Delhi, pp 107–111Google Scholar
  37. Lans CA (2006) Ethnomedicines used in trinidad and tobago for urinary problems and diabetes mellitus. J Ethnobiol Ethnomedicine 2:45–55CrossRefGoogle Scholar
  38. Latha PG, Panikkar KK (1998) Cytotoxic and antitumor principles from Ixora coccinea flowers. Cancer Lett 130(1–2):197–202CrossRefPubMedGoogle Scholar
  39. Li S, Yan T, Yang JQ, Oberley TD, Oberley LW (2000) The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Cancer Res 60(14):3927–3939PubMedGoogle Scholar
  40. Lopez-Lazaro M, Martin-Cordero C, Bermejo A, Cortes D, Ayuso MJ (2001) Cytotoxic compounds from Annonaceous species as DNA topoisomerase I poisons. Anticancer Res 21(5):3493–3497PubMedGoogle Scholar
  41. Magesh V, Venugopal R, Bhavani KD, Sakthisekaran D (2007) Effect of crocetin on benzo[a]pyrene induced lung carcinogenesis in swiss albino mice. Int J Cancer Res 3(3):143–150CrossRefGoogle Scholar
  42. Minari JB, Okeke U (2014) Chemopreventive effect of Annona muricata on DMBA-induced cell proliferation in the breast tissues of female albino rats. Egypt J Med Hum Genet 15(4):327–334CrossRefGoogle Scholar
  43. Misas C, Hernández N, Abraham A (1979) Biological evaluation of cuban plants. IV. Rev Cubana Med Trop 31(1):29–35Google Scholar
  44. Moghadamtousi SZ, Kadir HA, Paydar M, Rouhollahi E, Karimian H (2014) Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Alternat Med 14:299CrossRefGoogle Scholar
  45. Murray RK, Granner DK, Mayes PA, Rodwell VW (2003) Harper’s Illustrated Biochemistry, 26th edn. The McGraw-Hill Companies Inc, New YorkGoogle Scholar
  46. Notani PN (2001) Global variation in cancer incidence and mortality. Curr Sci 81(5):465–474Google Scholar
  47. Nwanjo HU, Oze GO (2007) Oxidative imbalance and non-enzymic antioxidant status in pulmonary tuberculosis infected. Pak J Nutr 6(6):590–592CrossRefGoogle Scholar
  48. OECD (2000) Guidance document on acute oral toxicity 425. Environmental health and safety monograph series on testing assessment No.24Google Scholar
  49. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358CrossRefPubMedGoogle Scholar
  50. Osborn MR, Beland FA, Harvey RG, Brookes P (1976) The reaction of (±)-7α, 8β-dihydroxy-9β, 10β-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with DNA. Int J Cancer 18(3):362–368CrossRefGoogle Scholar
  51. Owolabi MS, Ogundajo AL, Dosoky NS, Setzer WN (2013) The cytotoxic activity of Annona muricata leaf oil from Badagary, Nigeria. Am J Essent Oils Nat Prod 1(1):1–3Google Scholar
  52. Paulinus ON, Kinsley A, Ikechi EG (2013) Protective effect of ethanolic leaf extract of Annona muricata Linn. on some early events in cycas induced colorectal carcinogenesis in rats. J Pharm Sci Innov 2(4):14–21CrossRefGoogle Scholar
  53. Polshettiwar SA, Ganjiwale RO, Wadher SJ, Yeole PG (2007) Spectrophotometric estimation of total tannins in some ayurvedic eye drops. Indian J Pharma Sci 69(4):574–576CrossRefGoogle Scholar
  54. Price VE, Greenfield RE (1950) Anemia in cancer. In: Greenstein JP, Haddow A (eds) Advances in cancer research, vol 5. Academic Press, New York, pp 199–200Google Scholar
  55. Prieto P, Pineda M, Aguilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal Biochem 269(2):337–341CrossRefPubMedGoogle Scholar
  56. Rachmani EPN, Suhesti TS, Widiastuti R, Aditiyono (2012) Anticancer activity of leaf extract of Annona muricata against T47D cell line. Int J Appl Sci Technol 2(1):157–164Google Scholar
  57. Ramakrishnan G, Augustine TA, Jagan S, Vinodhkumar R, Devaki T (2007) Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Exp Oncol 29(1):39–44PubMedGoogle Scholar
  58. Rieser MJ, Fang XP, Rupprecht K, Hui YH, Smith DL, McLaughlin JL (1993) Bioactive single-ring acetogenins from seed extracts of Annona muricata. Planta Med 59(1):91–92CrossRefPubMedGoogle Scholar
  59. Rosenthaler K (1930) Chemical investigations of Plants. G Bell and sons, London.Google Scholar
  60. Roslida AH, Tay CE, Zuraini A, Chan PF (2010) Anti-inflammatory and anti-nociceptive activities of the ethanolic extract of Annona muricata leaf. J Nat Remedies 10(2):97–104Google Scholar
  61. Santos AFD, Sant’Ana AEG (2001) Molluscicidal properties of some species of Annona. Phytomedicine 8(2):115–120CrossRefPubMedGoogle Scholar
  62. Sharma P, Parmar J, Verma P, Sharma P, Goyal PK (2009) Anti-tumor activity of Phyllanthus niruri (a medicinal plant) on chemical-induced skin carcinogenesis in mice. Asian Pac J Cancer Prev 10(6):1089–1094PubMedGoogle Scholar
  63. Siegers CP and Younes M (1981) Effect of bioflavonoids on lipid peroxidation induced by glutathione depletion. Proc Int Bioflavonoid Symposium, Munich, FRG, pp 409Google Scholar
  64. Silalahi J (2006) Antioksidandalam diet dan karsinogenesis. Cermin Dunia Kedokteran 153:39–42Google Scholar
  65. Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 16(3):144–158Google Scholar
  66. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47(2):389–394CrossRefPubMedGoogle Scholar
  67. Slinkard K, Singleton VL (1977) Total phenol analysis: automation and comparison with manual methods. Am J Enol Vitic 28(1):49–55Google Scholar
  68. Sood R (1987) Textbook of medical laboratory technology, 2nd edn. Jaypee Publishers, New Delhi, pp 200–208Google Scholar
  69. Stefani ED, Boffetta P, Pellegrini HD, Mendilaharsu M, Carzoglio JC, Ronco A, Olivera L (1999) Dietary antioxidants and lung cancer risk: a case–control study in Uruguay. Nutr Cancer 34(1):100–110CrossRefPubMedGoogle Scholar
  70. Sundarrao K, Burrows I, Kuduk M (1993) Preliminary screening of anti-bacterial and anti-tumor activities of papuan new guinean active medicinal plants. Pharm Biol 31(1):3–6CrossRefGoogle Scholar
  71. Suyatmi, Suselo YH, Jusuf SA (2012) The selective cytotoxicity of ethanolic extract of Annona muricata leaf on HeLa Cervical cancer cells. International Conference: Research and Application on Traditional Complementary and Alternative Medicine in Health Care 24–27Google Scholar
  72. Tanaka T, Kojima T, Kawamori T, Wang A, Suzui M, Okamoto K, Mori H (1993) Inhibition of 4-nitroquinoline-1-oxide- induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. Carcinogenesis 14(7):1321–1325CrossRefPubMedGoogle Scholar
  73. Taylor L (2002) Technical data report for Graviola: Annona muricata. Herbal secrets of rain forest, secondth edn. Sage Press Inc, Austin, pp 1–6Google Scholar
  74. Wu FE, Zeng L, Gu ZM, Zhao GX, Zhang Y, Schwedler JT, McLaughlin JL, Sastrodihardjo S (1995) New bioactive monotetrahydrofuran annonaceous acetogenins, annomuricin C and muricatocin C from the leaves of Annona muricata. J Nat Prod 58(6):909–915CrossRefPubMedGoogle Scholar
  75. Yuan SS, Chang HL, Chen HW, Yeh YT, Kao YH, Lin KH, Wu YC, Su JH (2003) Annonacin, a mono-tetrahydrofuranacetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a bax- and caspase-3- related pathway. Life Sci 72(25):2853–2861CrossRefPubMedGoogle Scholar
  76. Yuan SS, Chang HL, Chen HW, Kuo FC, Liaw CC, Su JH, dan Wu YC (2006) Selective cytotoxicity of squamocin on T24 bladder cancer cells at the S PhaseVia a Bax-, Bad-, and caspase-3-related pathway. Life Sci 78(8):869–874CrossRefPubMedGoogle Scholar
  77. Zeng LU, Wu F-E, Oberlies NH, McLaughlin JL, Sastrodihadjo S (1996) Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata. J Nat Prod 59(11):1035–1042CrossRefPubMedGoogle Scholar

Copyright information

© Institute of Korean Medicine, Kyung Hee University and Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Department of PharmacologyJKK Nattraja College of PharmacyNamakkal districtIndia

Personalised recommendations