Comparison of Anticancer Properties of Annona muricata L. Acetonic and Methanolic Leaf Extracts

Author(s): Jéssica de Castro Nascimento, Rosa Maria do Vale Bosso, Maria Carolina Anholeti, Elaine da Silva Castro, Maximino Alencar Bezerra Junior, Thais Affonso do Nascimento, Selma Ribeiro de Paiva, Lidia Maria da Fonte de Amorim*.

Journal Name: The Natural Products Journal

Volume 9 , Issue 4 , 2019

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Abstract:

Background: Phytochemical studies of Annona muricata showed the presence of bioactive components with anticancer activity. We compared the anticancer properties of crude acetonic and methanolic A. muricata leaf extracts.

Methods: The viabilities of different cell lines (A549, U87, U251, K562 and VERO) treated with A. muricata acetonic or methanolic leaf extracts were measured using the MTT assay. Apoptosis induction, cell cycle and cytoskeleton rearrangements were evaluated in K562 by flow cytometry or fluorescence microscopy.

Results: Chemical analyses of the A. muricata extracts showed differences in their composition. The K562 cell line was the most sensitive to the treatment with the acetonic and methanolic extracts, and the IC50 values, respectively were 28.82 (24.41 - 34.69) and 32.49 (27.21 - 40.16) μg/mL. Both extracts induced apoptotic cell death and G0/G1 phase cell cycle arrest. For the first time, cytoskeleton rearrangements were observed in the K562 cell line treated with methanolic extract.

Conclusion: These findings suggest that both A. muricata extracts exhibit antileukemic potential and represent a promising source of novel compounds with anticancer activity.

Keywords: Graviola, leukemia, apoptosis, cell cycle arrest, cytoskeleton, K562 cell line.

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[2]
Mughal, T.I.; Radich, J.P.; Deininger, M.W.; Apperley, J.F.; Hughes, T.P.; Harrison, C.J.; Gambacorti-Passerini, C.; Saglio, G.; Cortes, J.; Daley, G.Q. Chronic myeloid leukemia: Reminiscences and dreams. Haematologica, 2016, 101(5), 541-558.
[http://dx.doi.org/10.3324/haematol.2015.139337] [PMID: 27132280]
[3]
Cortes, J.E.; Saglio, G.; Kantarjian, H.M.; Baccarani, M.; Mayer, J.; Boqué, C.; Shah, N.P.; Chuah, C.; Casanova, L.; Bradley-Garelik, B.; Manos, G.; Hochhaus, A. Final 5-year study results of DASISION: The dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J. Clin. Oncol., 2016, 34(20), 2333-2340.
[http://dx.doi.org/10.1200/JCO.2015.64.8899] [PMID: 27217448]
[4]
Cragg, G.M.; Newman, D.J. Natural products: A continuing source of novel drug leads. Biochim. Biophys. Acta -, General. Subjects, 2013, 1830(6), 3670-3695.
[5]
Deep, G.; Kumar, R.; Jain, A.K.; Dhar, D.; Panigrahi, G.K.; Hussain, A.; Agarwal, C.; El-Elimat, T.; Sica, V.P.; Oberlies, N.H.; Agarwal, R. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity. Sci. Rep., 2016, 6(23135), 23135.
[http://dx.doi.org/10.1038/srep23135] [PMID: 26979487]
[6]
Moghadamtousi, S.Z.; Fadaeinasab, M.; Nikzad, S.; Mohan, G.; Ali, H.M.; Kadir, H.A. Annona muricata (Annonaceae): A review of its traditional uses, isolated acetogenins and biological activities. Int. J. Mol. Sci., 2015, 16(7), 15625-15658.
[http://dx.doi.org/10.3390/ijms160715625] [PMID: 26184167]
[7]
Paul, J.; Gnanam, R.; Jayadeepa, R.M.; Arul, L. Anti cancer activity on Graviola, an exciting medicinal plant extract vs. various cancer cell lines and a detailed computational study on its potent anti-cancerous leads. Curr. Top. Med. Chem., 2013, 13(14), 1666-1673.
[http://dx.doi.org/10.2174/15680266113139990117] [PMID: 23889049]
[8]
Yang, C.; Gundala, S.R.; Mukkavilli, R.; Vangala, S.; Reid, M.D.; Aneja, R. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis, 2015, 36(6), 656-665.
[http://dx.doi.org/10.1093/carcin/bgv046] [PMID: 25863125]
[9]
Sun, S.; Liu, J.; Sun, X.; Zhu, W.; Yang, F.; Felczak, L.; Dou, P.Q.; Zhou, K. Novel Annonaceous Acetogenins from Graviola (Annona Muricata) fruits with strong anti-proliferative activity. Tetrahedron Lett., 2017, 58(19), 1895-1899.
[http://dx.doi.org/10.1016/j.tetlet.2017.04.016]
[10]
Torres, M.P.; Rachagani, S.; Purohit, V.; Pandey, P.; Joshi, S.; Moore, E.D.; Johansson, S.L.; Singh, P.K.; Ganti, A.K.; Batra, S.K. Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett., 2012, 323(1), 29-40.
[http://dx.doi.org/10.1016/j.canlet.2012.03.031] [PMID: 22475682]
[11]
Dai, Y.; Hogan, S.; Schmelz, E.M.; Ju, Y.H.; Canning, C.; Zhou, K. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr. Cancer, 2011, 63(5), 795-801.
[http://dx.doi.org/10.1080/01635581.2011.563027] [PMID: 21767082]
[12]
Gavamukulya, Y.; Abou-Elella, F.; Wamunyokoli, F.; El-Shemy, A.H. Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola) Asian Pac. J. Trop. Med, 2014, 7S1(S1), S355-S363.
[http://dx.doi.org/10.1016/S1995-7645(14)60258-3] [PMID: 25312150]
[13]
Syed Najmuddin, S.U.F.; Romli, M.F.; Hamid, M.; Alitheen, N.B.; Nik Abd Rahman, N.M. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line. BMC Complement. Altern. Med., 2016, 16(1), 311.
[http://dx.doi.org/10.1186/s12906-016-1290-y] [PMID: 27558166]
[14]
Zorofchian, M.S.; Karimian, H.; Rouhollahi, E.; Paydar, M.; Fadaeinasab, M.; Abdul, K.H. Annona muricata leaves induce G1cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells. J. Ethnopharmacol., 2014, 156, 277-289.
[15]
Pieme, C.A.; Kumar, S.G.; Dongmo, M.S.; Moukette, B.M.; Boyoum, F.F.; Ngogang, J.Y.; Saxena, A.K. Antiproliferative activity and induction of apoptosis by Annona muricata (Annonaceae) extract on human cancer cells. BMC Complement. Altern. Med., 2014, 14(516), 516.
[http://dx.doi.org/10.1186/1472-6882-14-516] [PMID: 25539720]
[16]
Kuete, V.; Dzotam, J.K.; Voukeng, I.K.; Fankam, A.G.; Efferth, T. Cytotoxicity of methanol extracts of Annona muricata, Passiflora edulis and nine other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines. Springerplus, 2016, 5(1), 1666.
[http://dx.doi.org/10.1186/s40064-016-3361-4] [PMID: 27730025]
[17]
Ezirim, A.U.; Okochi, V.I.; James, A.B.; Adebeshi, O.A.; Ogunnowo, S.O. Induction of apoptosis in myelogenous leukemic K562 cells by ethanolic leaf extract of Annona muricata L. Glob. J. Res. Med. Plants Indig. Med., 2013, 2(3), 142-151.
[18]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[19]
Telford, W.G.; King, L.E.; Fraker, P.J. Comparative evaluation of several DNA binding dyes in the detection of apoptosis-associated chromatin degradation by flow cytometry. Cytometry, 1992, 13(2), 137-143.
[http://dx.doi.org/10.1002/cyto.990130205] [PMID: 1372208]
[20]
Baskić, D.; Popović, S.; Ristić, P.; Arsenijević, N.N. Analysis of cycloheximide-induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol. Int., 2006, 30(11), 924-932.
[http://dx.doi.org/10.1016/j.cellbi.2006.06.016] [PMID: 16895761]
[21]
Chiang, L.C.; Chiang, W.; Chang, M.Y.; Ng, L.T.; Lin, C.C. Antileukemic activity of selected natural products in Taiwan. Am. J. Chin. Med., 2003, 31(1), 37-46.
[http://dx.doi.org/10.1142/S0192415X03000825] [PMID: 12723753]
[22]
Figueiredo, E.R.; Vieira, I.J.C.; De Souza, J.J.; Braz-Filho, R.; Mathias, L.; Kanashiro, M.M.; Côrtes, F.H. Isolation, identification and evaluation of antileukemic activity of monoterpenic indole alkaloids of Tabernaemontana salzmannii (A. DC.). Apocynaceae. Brazilian J. Pharmacogn., 2010, 20(5), 675-681.
[http://dx.doi.org/10.1590/S0102-695X2010005000019]
[23]
Moghadamtousi, S.Z.; Kadir, H.A.; Paydar, M.; Rouhollahi, E.; Karimian, H. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement. Altern. Med., 2014, 14(1), 299.
[http://dx.doi.org/10.1186/1472-6882-14-299] [PMID: 25127718]
[24]
Badisa, R.B.; Ayuk-Takem, L.T.; Ikediobi, C.O.; Walker, E.H. Selective anticancer activity of pure licamichauxiioic-B acid in cultured cell lines. Pharm. Biol., 2006, 44(2), 141-145.
[http://dx.doi.org/10.1080/13880200600592301]
[25]
Boichuk, S.; Galembikova, A.; Zykova, S.; Ramazanov, B.; Khusnutdinov, R.; Dunaev, P.; Khaibullina, S.; Lombardi, V. Ethyl-2-amino-pyrrole-3-carboxylates are novel potent anticancer agents that affect tubulin polymerization, induce G2/M cell-cycle arrest, and effectively inhibit soft tissue cancer cell growth in vitro. Anticancer Drugs, 2016, 27(7), 620-634.
[http://dx.doi.org/10.1097/CAD.0000000000000372] [PMID: 27129079]
[26]
Evan, G.I.; Vousden, K.H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411(6835), 342-348.
[http://dx.doi.org/10.1038/35077213] [PMID: 11357141]
[27]
Hassan, M.; Watari, H.; AbuAlmaaty, A.; Ohba, Y.; Sakuragi, N. Apoptosis and molecular targeting therapy in cancer. BioMed Res. Int., 2014, 2014150845
[http://dx.doi.org/10.1155/2014/150845] [PMID: 25013758]
[28]
Zivny, J.; Klener, P.; Pytlik, R.; Andera, L. The role of apoptosis in cancer development and treatment: Focusing on the development and treatment of hematologic malignancies. Curr. Pharm. Des., 2010, 16(1), 11-33.
[http://dx.doi.org/10.2174/138161210789941883] [PMID: 20214615]
[29]
Pellegrini, F.; Budman, D.R. Review: Tubulin function, action of antitubulin drugs, and new drug development. Cancer Invest., 2005, 23(3), 264-273.
[http://dx.doi.org/10.1081/CNV-200055970] [PMID: 15948296]
[30]
Jordan, M.A.; Horwitz, S.B.; Lobert, S.; Correia, J.J. Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine. Semin. Oncol., 2008, 35(3), S6-S12.
[http://dx.doi.org/10.1053/j.seminoncol.2008.01.009] [PMID: 18538179]
[31]
Oropesa-Ávila, M.; Fernández-Vega, A.; De La Mata, M.; Maraver, J.G.; Cordero, M.D.; Cotán, D.; de Miguel, M.; Calero, C.P.; Paz, M.V.; Pavón, A.D.; Sánchez, M.A.; Zaderenko, A.P.; Ybot-González, P.; Sánchez-Alcázar, J.A. Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis. Cell Death Dis., 2013, 4(3) e527
[http://dx.doi.org/10.1038/cddis.2013.58] [PMID: 23470534]
[32]
Berges, R.; Balzeau, J.; Peterson, A.C.; Eyer, J. A tubulin binding peptide targets glioma cells disrupting their microtubules, blocking migration, and inducing apoptosis. Mol. Ther., 2012, 20(7), 1367-1377.
[http://dx.doi.org/10.1038/mt.2012.45] [PMID: 22491214]


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Article Details

VOLUME: 9
ISSUE: 4
Year: 2019
Page: [312 - 320]
Pages: 9
DOI: 10.2174/2210315509666181203125608
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