Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells

BMC Complementary and Alternative Medicine - Tập 13 - Trang 1-8 - 2013
Victor Kuete1,2, Igor K Voukeng2, Roger Tsobou3, Armelle T Mbaveng2, Benjamin Wiench1, Veronique P Beng4, Thomas Efferth1
1Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany
2Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
3Department of Plant Biology, Faculty of Science, University of Dschang, Dschang, Cameroon
4Department of Organic Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon

Tóm tắt

Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines. The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay. A preliminary assay on leukemia CCRF-CEM cells at 40 μg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC50 values below or around 30 μg/mL against the nine tested cancer cell lines. The lowest IC50 value of 8.40 μg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC50 values below 10 μg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53+/+ and HCT116p53-/- colon cancer cells and E. abyssinica against HCT116 p53+/+ cells. The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines.

Tài liệu tham khảo

Liu J, Zhao Y, Guo Q, Wang Z, Wang H, Yang Y, Huang Y: TAT-modified nanosilver for combating multidrug-resistant cancer. Biomaterials. 2012, 33 (26): 6155-6161. 10.1016/j.biomaterials.2012.05.035. Broxterman H, Gotink K, Verheul H: Understanding the causes of multidrug resistance in cancer: a comparison of doxorubicin and sunitinib. Drug Resist Update. 2009, 12: 114-126. 10.1016/j.drup.2009.07.001. Newman DJ, Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007, 70 (3): 461-477. 10.1021/np068054v. Stevigny C, Bailly C, Quetin-Leclercq J: Cytotoxic and antitumor potentialities of aporphinoid alkaloids. Curr Med Chem Anticancer Agents. 2005, 5 (2): 173-182. 10.2174/1568011053174864. Adjanohoun J, Aboubakar N, Dramane K, Ebot M, Ekpere J, Enow-Orock E, Focho D, Gbile Z, Kamanyi A, Kamsu-Kom J: Traditional medicine and pharmacopoeia: contribution to ethnobotanical and floristic studies in Cameroon. 1996, Lagos-Nigeria: Technical and Research Commission of Organisation of African Unity (OAU/STRC) Kuete V, Mbaveng AT, Tsaffack M, Beng VP, Etoa FX, Nkengfack AE, Meyer JJM, Lall N: Antitumor, antioxidant and antimicrobial activities of Bersama engleriana (Melianthaceae). J Ethnopharmacol. 2007, 115 (3): 494-501. Kuete V, Krusche B, Youns M, Voukeng I, Fankam AG, Tankeo S, Lacmata S, Efferth T: Cytotoxicity of some Cameroonian spices and selected medicinal plant extracts. J Ethnopharmacol. 2011, 134 (3): 803-812. 10.1016/j.jep.2011.01.035. Dzoyem JP, Nkuete AH, Kuete V, Tala MF, Wabo HK, Guru SK, Rajput VS, Sharma A, Tane P, Khan IA: Cytotoxicity and antimicrobial activity of the methanol extract and compounds from Polygonum limbatum. Planta Med. 2012, 78 (8): 787-792. Choumessi AT, Danel M, Chassaing S, Truchet I, Penlap VB, Pieme AC, Asonganyi T, Ducommun B, Valette A: Characterization of the antiproliferative activity of Xylopia aethiopica. Cell Div. 2012, 7 (1): 8-10.1186/1747-1028-7-8. Dzoyem J, Guru S, Pieme C, Kuete V, Sharma A, Khan I, Saxena A, Vishwakarma R: Cytotoxic and antimicrobial activity of selected Cameroonian edible plants. BMC Complement Altern Med. 2013, 13 (1): 78-10.1186/1472-6882-13-78. Tamokou Jde D, Chouna J, Fischer-Fodor E, Chereches G, Barbos O, Damian G, Benedec D, Duma M, Efouet A, Wabo H: Anticancer and antimicrobial activities of some antioxidant-rich cameroonian medicinal plants. PLoS One. 2013, 8 (2): e55880-10.1371/journal.pone.0055880. Kuete V, Sandjo L, Wiench B, Efferth T: Cytotoxicity and modes of action of four Cameroonian dietary spices ethno-medically used to treat Cancers: Echinops giganteus, Xylopia aethiopica, Imperata cylindrica and Piper capense. J Ethnopharmacol. 2013, doi. 10.1016/j.jep.2013.06.029 Okunade AL: Ageratum conyzoides L. (Asteraceae). Fitoterapia. 2002, 73 (1): 1-16. 10.1016/S0367-326X(01)00364-1. Rukunga GM, Waterman PG: A new oleanane glycoside from the stem bark of Albizia gummifera. Fitoterapia. 2001, 72 (2): 140-145. 10.1016/S0367-326X(00)00276-8. Rukunga GM, Muregi FW, Tolo FM, Omar SA, Mwitari P, Muthaura CN, Omlin F, Lwande W, Hassanali A, Githure J, Iraqi FW, Mungai GM, Kraus W, Kofi-Tsekpo : The antiplasmodial activity of spermine alkaloids isolated from Albizia gummifera. Fitoterapia. 2007, 78 (7–8): 455-459. Boudreau MD, Beland FA: An evaluation of the biological and toxicological properties of Aloe barbadensis (miller), Aloe vera. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2006, 24 (1): 103-154. 10.1080/10590500600614303. Jainu M, Devi S: In vitro and in vivo evaluation of free radical scavenging potential of Cissus quadrangularis. Afr J Biomed Res. 2005, 8: 95-99. Jainu M, Devi CS: Gastroprotective action of Cissus quadrangularis extract against NSAID induced gastric ulcer: role of proinflammatory cytokines and oxidative damage. Chem Biol Interact. 2006, 161 (3): 262-270. 10.1016/j.cbi.2006.04.011. Berkov S, Romani S, Herrera M, Viladomat F, Codina C, Momekov G, Ionkova I, Bastida J: Antiproliferative alkaloids from Crinum zeylanicum. Phytother Res. 2011, 25 (11): 1686-1692. 10.1002/ptr.3468. Kapingu C, Guillaume D, Mbwambo H, Moshi J, Uliso C, Mahunnah A: Diterpenoids from the roots of Croton macrostachys. Phytochemistry. 2000, 54: 767-770. 10.1016/S0031-9422(00)00166-7. Gao H, Kuroyanagi M, Wu L, Kawahara N, Yasuno T, Nakamura Y: Antitumor-promoting constituents from Dioscorea bulbifera L. in JB6 mouse epidermal cells. Biol Pharm Bull. 2002, 25 (9): 1241-1243. 10.1248/bpb.25.1241. Kuete V, Betrandteponno R, Mbaveng AT, Tapondjou LA, Meyer JJ, Barboni L, Lall N: Antibacterial activities of the extracts, fractions and compounds from Dioscorea bulbifera. BMC Complement Altern Med. 2012, 12: 228-10.1186/1472-6882-12-228. Mbiantcha M, Kamanyi A, Teponno RB, Tapondjou AL, Watcho P, Nguelefack TB: Analgesic and anti-inflammatory properties of extracts from the bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in mice and rats. Evid Based Complement Alternat Med. 2011, 2011: 912935- Corley G, Tempesta S: Convulsant alkaloids from Dioscorea dumetorum. Tetrahedron Lett. 1985, 26 (13): 1615-1618. 10.1016/S0040-4039(00)98566-6. Adesanya S, Ogundana S, Roberts M: Dihydrostilbene phytoalexins from Dioscorea bulbifera and D. dumentorum. Phytochemistry. 1989, 28 (3): 773-774. 10.1016/0031-9422(89)80113-X. Eno A, Azah N: Effect of ethanolic extract from Elaeophorbia drupifera leaves on the gastrointestinal smooth muscle of the rabbit. Niger J Physiol Sci. 2004, 19 (1–2): 60-68. Kinghorn A, Evans F: Occurrence of ingenol in Elaeophorbia species. Planta Med. 1974, 26: 150-154. 10.1055/s-0028-1097982. Ahiahonu PW, Goodenowe DB: Triterpenoids from leaves of Elaeophorbia drupifera. Fitoterapia. 2007, 78 (5): 337-341. 10.1016/j.fitote.2007.02.002. Ayisi N, Nyadedzor C: Comparative in vitro effects of AZT and extract of Ocimum gratissimum, Ficus polita, Clausena anisata, Alchornea cordifolia, and Elaeophorbia drupifera against HIV-1 and HIV-2 infections. Antivir Res. 2003, 58: 25-33. 10.1016/S0166-3542(02)00166-3. Eno AE, Owo OI: Cardiovascular effects of an extract from the roots of a shrub Elaeophorbia drupifera. Phytother Res. 1999, 13 (7): 549-554. 10.1002/(SICI)1099-1573(199911)13:7<549::AID-PTR464>3.0.CO;2-Q. Olajide OA, Alada AR: Studies on the anti-inflammatory properties of Entada abyssinica. Fitoterapia. 2001, 72 (5): 492-496. 10.1016/S0367-326X(01)00273-8. Oben J, Assi S, Agbor G, Musoro D: Effect of Eremomastax speciosa on experimantal diarrhoea. Afr J Trad Complement Altern Med. 2006, 3 (1): 95-100. Essien E, Aboaba O, Ogunwande A: Constituents and antimicrobial properties of the leaf essential oil of Gossypium barbadense (Linn.). J Med Plant Res. 2011, 5: 702-705. Stipanovic D, Bell A, Mace E, Howell R: Antimicrobial terpenoids of Gossypium: 6-methoxygossypol and 6,6′-dimethoxygossypol. Phytochemistry. 1975, 14: 1077-1081. 10.1016/0031-9422(75)85190-9. Bell A, Stipanovic D, Howell R, Fryxell A: Antimicrobial terpenoids of Gossypium: Hemigossypol, 6-methoxyhemigossypol and 6-deoxyhemigossypol. Phytochemistry. 1975, 14: 225-231. 10.1016/0031-9422(75)85044-8. Saini S, Kaur H, Verma B, Ripudaman , Singh K: Kigelia africana (Lam.) Benth: - an overview. Nat Prod Rad. 2009, 8 (2): 190-197. Aladesanmi A, Iwalewa E, Adebajo A, Akinkunmi E, Taiwo B, Olorunmola F, Lamikanra A: Antimicrobial and antioxidant activities of some Nigerian medicinal plants. Afr J Trad Complement Altern Med. 2007, 4 (2): 173-184. Tantangmo F, Lenta BN, Boyom FF, Ngouela S, Kaiser M, Tsamo E, Weniger B, Rosenthal PJ, Vonthron-Senecheau C: Antiprotozoal activities of some constituents of Markhamia tomentosa (Bignoniaceae). Ann Trop Med Parasitol. 2010, 104 (5): 391-398. 10.1179/136485910X12743554760180. Okpekon T, Yolou S, Gleye C, Roblot F, Loiseau P, Bories C, Grellier P, Frappier F, Laurens A, Hocquemiller R: Antiparasitic activities of medicinal plants used in Ivory Coast. J Ethnopharmacol. 2004, 90 (1): 91-97. 10.1016/j.jep.2003.09.029. Miemanang R, Krohn K, Hussain H, Dongo E: Paullinoside a and paullinomide a: a new cerebroside and a new ceramide from leaves of Paullinia pinnata. Z Naturforsch. 2006, 61b: 1123-1127. Akinpelu DA, Obuotor EM: Antibacterial activity of Piliostigma thonningii stem bark. Fitoterapia. 2000, 71 (4): 442-443. 10.1016/S0367-326X(00)00136-2. Ibewuike JC, Ogundaini AO, Ogungbamila FO, Martin M-T, Gallard J-F, Bohlin L, Païs M: Piliostigmin, a 2-phenoxychromone, and C-methylflavonols from Piliostigma thonningii. Phytochemistry. 1996, 43 (3): 687-690. 10.1016/0031-9422(96)00367-6. Pianaro A, Pinto P, Ferreira T, Ishikawa K, Braz-Filho R: Iridoid glucoside and antifungal phenolic compounds from Spathodea campanulata roots. Semina: Ciências Agrárias, Londrina. 2007, 28 (2): 251-256. Simbo D: An ethnobotanical survey of medicinal plants in Babungo, Northwest Region. Cameroon. Ethnobiol Ethnomed. 2010, 6: 8-10.1186/1746-4269-6-8. Ekor M, Ashorobi R, Ibitoye SF, Kasimi L: Acute toxicity, analgesic potential and preliminary antimocrobial studies of the aqueous plant extract of Spilanthes filicaulis. Niger J Health Biomed Sci. 2005, 4 (1): 30-34. Tan V, Njimi K, Ayafor F: Screening of some African Medicinal plants for antiulcerogenic activity: part 1. Phytother res. 1997, 11: 45-47. 10.1002/(SICI)1099-1573(199702)11:1<45::AID-PTR945>3.0.CO;2-I. Ramsay KS, Wafo P, Ali Z, Khan A, Oluyemisi OO, Marasini BP, Khan IA, Bonaventure NT, Choudhary MI, Atta ur R: Chemical constituents of Stereospermum acuminatissimum and their urease and alpha-chymotrypsin inhibitions. Fitoterapia. 2012, 83 (1): 204-208. 10.1016/j.fitote.2011.10.014. Sob SV, Wabo HK, Tang CP, Tane P, Ngadjui BT, Ye Y: Phenol esters and other constituents from the stem barks of Stereospermum acuminatissimum. J Asian Nat Prod Res. 2011, 13 (12): 1128-1134. 10.1080/10286020.2011.619182. Ndjakou LB, Vonthron-Sénécheau C, Fongang Soh R, Tantangmo F, Ngouela KM, Tsamo E, Anton R, Weniger B: In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants. J Ethnopharmacol. 2007, 111 (1): 8-12. 10.1016/j.jep.2006.10.036. Atta-ur-Rahman , Zareen S, Choudhary I, Akhtar N, Shujaat S, Ngounou N: Some chemical constituents of Terminalia glaucescens and their enzymes inhibition activity. Z Naturforsch. 2005, 60b: 347-350. Adebayo E, Ishola O: Phytochemical and antimicrobial screening of crude extracts from the root, stem bark, and leaves of Terminalia glaucescens. Afr J Pharm Pharmacol. 2009, 3 (5): 217-221. Kimmig A, Gekeler V, Neumann M, Frese G, Handgretinger R, Kardos G, Diddens H, Niethammer D: Susceptibility of multidrug-resistant human leukemia cell lines to human interleukin 2-activated killer cells. Cancer Res. 1990, 50 (21): 6793-6799. Efferth T, Sauerbrey A, Olbrich A, Gebhart E, Rauch P, Weber HO, Hengstler JG, Halatsch ME, Volm M, Tew KD, Ross DD, Funk JO: Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol. 2003, 64 (2): 382-394. 10.1124/mol.64.2.382. Gillet J, Efferth T, Steinbach D, Hamels J, de Longueville F, Bertholet V, Remacle J: Microarray-based detection of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes. Cancer Res. 2004, 64 (24): 8987-8993. 10.1158/0008-5472.CAN-04-1978. Huang HS, Nagane M, Klingbeil CK, Lin H, Nishikawa R, Ji XD, Huang CM, Gill GN, Wiley HS, Cavenee WK: The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol Chem. 1997, 272 (5): 2927-2935. 10.1074/jbc.272.5.2927. O’Brien J, Wilson I, Orton T, Pognan F: Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem. 2000, 267 (17): 5421-5426. 10.1046/j.1432-1327.2000.01606.x. Suffness M, Pezzuto JM: Assays related to cancer drug discovery. Methods in Plant Biochemistry: Assays for Bioactivity. Edited by: Hostettmann K. 1990, London: Academic Press, 6- Longley D, Johnston P: Molecular mechanisms of drug resistance. J Pathol. 2005, 205: 275-292. 10.1002/path.1706. Kuete V, Efferth T: Pharmacogenomics of Cameroonian traditional herbal medicine for cancer therapy. J Ethnopharmacol. 2011, 137 (1): 752-766. 10.1016/j.jep.2011.06.035. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/13/250/prepub