Indian Journal of Drugs and Diseases

Open Access Open Access  Restricted Access Subscription Access

Induction of Apoptosis in Myelogenous Leukemic K562 Cells by Ethanolic Leaf Extract of Annona muricata


Affiliations
1 Department of Biochemistry, University of Lagos, Akoka, Nigeria
2 Department of Cell biology, University of Lagos, Akoka, Nigeria
3 Department of Biochemistry, University of Port Harcourt, Rivers State, Nigeria
 

Prevalence of cancer, especially in Nigeria, is silently growing at exponential rates due to its nature and numerous risk factors associated with its development. Most chemotherapeutic drugs used today are expensive and toxic to normal cells, hence the need for alternative treatment options. In this present study, the efficacy of ethanolic extracts of Annona muricata leaves for its cytotoxicity potential and induction of apoptosis in K562 cancer cells, was investigated. Phytochemical screening verified presence of alkaloids, tannins, flavonoids, saponins, anthraquinones and cardiac glycosides. Using Neutral red uptake assay, the ethanolic extract showed peak cytotoxicity levels (PAnnona muricata induced apoptosis in the myelogenous leukemic K562 cell line. This supports the therapeutic application of Annona muricata to be considered as a natural product source for the development of pro-apoptotic drugs.

Keywords

Apoptosis, K562 Cells, Annona Muricata
User
Notifications

  • Adeyemi OD, Komolafe OA, Adewole OS, Obuotor EM and Adenowo KT (2009a) Anti Hyperglycemic activities of Annona muricata. Afr. J. Tradit. Complement Altern. Med. 6(1), 62-69

  • Adeyemi OD, Komolafe OA, Adewole OS and Obuotor EM (2009b) Anti Hyperlipidemic activities of Annona muricata. The Internet J. Alternative Med. 7, 1

  • Alali FQ, Kaakeh W, Bennett GW and McLaughlin JL (1998) Annonaceous acetogenins as natural pesticides; potent toxicity against insecticide-susceptible and resistant german cockroaches (Dictyoptera: blattellidae). J. Econ. Entomol. 91(3), 641-649

  • Alali FQ, Liu XX and McLaughlin JL (1999) Annonaceous acetogenins: recent progress. J. Nat. Prod. 62(3), 504-540

  • Antoun MD, Gerena L, and Milhous WK (1993) Screening of the flora of Puerto Rico for potential antimalarial bioactives. Int. J. Pharmacog. 31(4), 255-259

  • Antoun MD, Martinez E, Caballero R, Oquendo I, Proctor GR, Weislow OS, McCloud TG, Kiser R, Staley P, and Clanton D (1999) Evaluation of the flora of Puerto Rico for in vitro cytotoxic and anti-HIV activities. Pharmaceutical Biol. 37(4), 277-280

  • Borenfreund E and Puerner JA (1984) A simple quantitative procedure using monolayer culture for toxicity assays. J. Tissue Cult. Meth. 9,7-9

  • Bories C, Loiseau P, Cortes D, Myint SH, Hocquemiller R, Gayral P, Cavé A and Laurens A (1991) Antiparasitic activity of Annona muricata and Annona cherimolia seeds. Planta Med. 57(5), 434-436

  • Carbajal D, Casaco A, Arruzazabala L, Gonzalez R and Fuentes V (1991) Pharmacological screening of plant decoctions commonly used in Cuban folk medicine. J. Ethnopharmacol. 33(1/2), 21-24

  • Craig R and Stitzel H (2003) Modern pharmacology with clinical applications. 5th ed. Lippincott Williams and Wilkins edition. pp: 631-633

  • Crow MT, Mani K, Nam YJ and Kitsis RN (2004) The mitochondrial death pathway and cardiac myocyte apoptosis. Circ. Res. 95(10), 957-970

  • de Feo V (1992) Medicinal plants of the Andes Peru. Fitoterapia 63,417-440

  • Gbeassor M, Kedjagni AY, Koumaglo K, de Souza C, Agbo K, Aklikokou K, and Amegbo KA (1990) In vitro antimalarial activity of six medicinal plants.” Phytother. Res. 4(3), 115-117

  • Guadano A, Carmen G, Eduardo P, Cortes D and González-Coloma A (2000) “Insecticidal and mutagenic evaluation of two annonaceous acetogenins.” J. Nat. Prod. 63(6), 773-776

  • Heatwole VM (1999) TUNEL Assay for apoptotic cells. Mol.Biol. 115 (111), 141-148.

  • Jaramillo MC, Arango GJ, González MC, Robledo SM and Velez ID (2000) Cytotoxicity and antileishmanial activity of Annona muricata pericarp Fitoterapia. 71(2), 183-186

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D (2011) Global cancer statistics. CA Cancer J. for clinicians 61 (2), 134

  • Johnstone RW, Ruefli AA and Lowe SW (2000) Apoptosis: A link between cancer genetics and chemotherapy. Cell 108, 153-164

  • Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL and Jameson JL (2005) Harrison’s Principle of Internal Medicine. 16th ed. McGraw-Hill companies, Inc. USA. pp: 630

  • Khan MR (1998) Antibacterial activity of some annonaceae Part I. Fitoterapia 69(4), 367-369

  • Khan MR and Mlungwana SM (1999) C-sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia africana. Fitoterapia 70, 96-97

  • Kilham EL (1999) Evaluating A Health Service at a primary care clinic in Chilamanca, Bolivia. Social Sci. Med. 49, 663-678

  • Kojima N and Tanaka T (2009) Medicinal chemistry of Annonaceous Acetogenins: Design, synthesis, and biological evaluation of novel analogues Molecules 14, 3621-3661

  • Liaw CC (2002) New cytotoxic monotetrahydrofuran Annonaceous acetogenins from Annona muricata. J. Nat. Prod. 65(4),470-475

  • Lozzio BB, Lozzio CB, Bamberger EG, Feliu AS (1981) A multipotential leukaemia cell line (K-562) of human origin. Proc. Society for Experimental Biol. & Med. 166, 546-550

  • Mathers CD, Boschi-Pinto C, Lopez AD and Murray CJL (2001) Cancer incidence, mortality and survival by site for 14 regions of the world. World Health Organization. http://www.who.int/entity/healthinfo/paper13.pdf.

  • Morré DJ, de Cabo R, Farley C, Oberlies NH and McLaughlin JL (1995) Mode of action of bullatacin, a potent antitumor acetogenin: Inhibition of NADH oxidase activity of Hela and HL-60, but not liver, plasma membranes. Life Sci. 56, 343-348

  • N’Gouemo P, Koudogbo B, Tchivounda PH, Akono-Nguema C and Etoua MM (1997) Effects of ethanol extract of Annona muricata on pentylenetetrazol-induced convulsive seizures in mice. Phytother. Res. 11(3), 243-245

  • Oberlies NH, Croy VL, Harrison ML and McLaughlin JL (1997) The annonaceous acetogenin bullatacin is cytotoxic against multidrug-resistant human mammary adenocarcinoma cells. Cancer Lett. 115, 73-79

  • Pirnia F, Schneider E, Betticher DC and Borner MM (2002) Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3 and Fas-independent pathway. Cell Death Differ. 9(9),905-914

  • Santos AF and Sant’Ana AEG (2001) Molluscicidal properties of some species of Annona. Phytomedicine 8(2), 115-120

  • Shafi G, Anjana M, Hasan T, Alshatwi A and Jyothy A and Lei DK (2009) Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella Sativa. Cancer cell Int. 9,29

  • Trease and Evans (1989) Pharmacognosy. 14th ed. Evans edition, WB Saunder company Ltd. London.

  • Vasques MR (1990) Useful plants of Amanzonian Peru. Second Draft Field with USDA‘s National Agricultural Library. USA

  • Wyllie AH (1997) Apoptosis: An overview. British Medical Bulletin 53, 451-465

  • Yang H, Zhang N, Li X, Chen J and Cai B (2009) Structure-activity relationships of diverse annonaceous acetogenins against human tumor cells. Bioorg. Med. Chem. Lett.19 (8), 2199-2202

  • Yuan SF (2003) Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cellsat the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway. Life Sci. 72, 2853-2861

  • Zafra-Polo MC, Figadère B, Gallardo T, Tormo JR and Cortes D (1998) Natural acetogenins from annonaceae, synthesis and mechanisms of action. Phytochem. 48: 1087-1117

  • Zeng L and McLaughlin JL (1996) Recent advances in Annonaceous acetogenins. Nat. Prod. Rep. 13(4), 275-306


Abstract Views: 1091

PDF Views: 622




  • Induction of Apoptosis in Myelogenous Leukemic K562 Cells by Ethanolic Leaf Extract of Annona muricata

Abstract Views: 1091  |  PDF Views: 622

Authors

A. U. Ezirim
Department of Biochemistry, University of Lagos, Akoka, Nigeria
V. I. Okachi
Department of Biochemistry, University of Lagos, Akoka, Nigeria
A. B. James
Department of Biochemistry, University of Lagos, Akoka, Nigeria
O. A. Adebeshi
Department of Cell biology, University of Lagos, Akoka, Nigeria
S. Ogunnowo
Department of Biochemistry, University of Lagos, Akoka, Nigeria
O. B. Odeghe
Department of Biochemistry, University of Port Harcourt, Rivers State, Nigeria

Abstract


Prevalence of cancer, especially in Nigeria, is silently growing at exponential rates due to its nature and numerous risk factors associated with its development. Most chemotherapeutic drugs used today are expensive and toxic to normal cells, hence the need for alternative treatment options. In this present study, the efficacy of ethanolic extracts of Annona muricata leaves for its cytotoxicity potential and induction of apoptosis in K562 cancer cells, was investigated. Phytochemical screening verified presence of alkaloids, tannins, flavonoids, saponins, anthraquinones and cardiac glycosides. Using Neutral red uptake assay, the ethanolic extract showed peak cytotoxicity levels (PAnnona muricata induced apoptosis in the myelogenous leukemic K562 cell line. This supports the therapeutic application of Annona muricata to be considered as a natural product source for the development of pro-apoptotic drugs.

Keywords


Apoptosis, K562 Cells, Annona Muricata

References