Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

In vitro cytotoxic activity of medicinal plants from Nigeria ethnomedicine on Rhabdomyosarcoma cancer cell line and HPLC analysis of active extracts

Authors: Omonike O. Ogbole, Peter A. Segun, Adekunle J. Adeniji

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Cancer is a leading cause of death world-wide, with approximately 17.5 million new cases and 8.7 million cancer related deaths in 2015. The problems of poor selectivity and severe side effects of the available anticancer drugs, have demanded the need for the development of safer and more effective chemotherapeutic agents. The present study was aimed at determining the cytotoxicities of 31 medicinal plants extracts, used in Nigerian ethnomedicine for the treatment of cancer.

Methods

The plant extracts were screened for cytotoxicity, using the brine shrimp lethality assay (BSLA) and MTT cytotoxicity assay. Rhabdomyosarcoma (RD) cell line, normal Vero cell line and the normal prostate (PNT2) cell line were used for the MTT assay, while Artemia salina nauplii was used for the BSLA. The phytochemical composition of the active plant extracts was determined by high performance liquid chromatography (HPLC) analysis.

Results

The extract of Eluesine indica (L.) Gaertn (Poaceae), with a LC50 value of 76.3 μg/mL, had the highest cytotoxicity on the brine shrimp larvae compared to cyclophosphamide (LC50 = 101.3 μg/mL). Two plants extracts, Macaranga barteri Mull. Arg. (Euphorbiaceae) and Calliandra portoricensis (Jacq.) Benth (Leguminosae) exhibited significant cytotoxic activity against the RD cell line and had comparable lethal activity on the brine shrimps. Further cytotoxic investigation showed that the dichloromethane fraction of Macaranga barteri (DMB) and the ethyl acetate fraction of Calliandra portoricensis (ECP), exhibited approximately 6-fold and 4-fold activity, respectively, compared to cyclophosphamide on RD cell line. Determination of selective index (SI) using Vero and PNT2 cell line indicated that DMB and ECP displayed a high degree of selectivity against the cancer cell under investigation. HPLC analysis showed that 3,5dicaffeoylquinic acid, acteoside, kampferol-7-O-glucoside and bastadin 11 were the major components of DMB while the major components of ECP were neurolenin B, nigrosporolide and trans-geranic acid.

Conclusion

The results demonstrate the cytotoxicity of Macaranga barteri and Calliandra portoricensis extracts, which are used in Nigerian folklore for cancer treatment.
Literature
1.
go back to reference Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncology. 2017;3(4):524–48.PubMedCrossRef Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncology. 2017;3(4):524–48.PubMedCrossRef
2.
go back to reference Sylla BS, Wild CP. A million Africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer. 2012;130(2):245–50.PubMedCrossRef Sylla BS, Wild CP. A million Africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer. 2012;130(2):245–50.PubMedCrossRef
3.
go back to reference Popoola A, Omodele F, Oludara M, Ibrahim N, Igwilo A, Makanjuola S. Prevalence and pattern of cancers among adults attending a tertiary health institution in Lagos. Nigeria IOSR-JDMS. 2013;6(3):68–73.CrossRef Popoola A, Omodele F, Oludara M, Ibrahim N, Igwilo A, Makanjuola S. Prevalence and pattern of cancers among adults attending a tertiary health institution in Lagos. Nigeria IOSR-JDMS. 2013;6(3):68–73.CrossRef
4.
go back to reference Ognjanovic S, Linabery AM, Charbonneau B, Ross JA. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer. 2009;115(18):4218–26.PubMedPubMedCentralCrossRef Ognjanovic S, Linabery AM, Charbonneau B, Ross JA. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer. 2009;115(18):4218–26.PubMedPubMedCentralCrossRef
5.
go back to reference Mandong BM, Ngbea JA. Childhood rhabdomyosarcoma: a review of 35 cases and literature. Niger. J. Med.:J. Natl. Assoc. Resident Doct. Niger. 2011;20(4):466. Mandong BM, Ngbea JA. Childhood rhabdomyosarcoma: a review of 35 cases and literature. Niger. J. Med.:J. Natl. Assoc. Resident Doct. Niger. 2011;20(4):466.
6.
go back to reference Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2104. J Nat Prod. 2016;79:629–61.PubMedCrossRef Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2104. J Nat Prod. 2016;79:629–61.PubMedCrossRef
7.
go back to reference Ogbourne SM, Parsons PG. The value of nature's natural product library for the discovery of new chemical entities: the discovery of ingenol mebutate. Fitoterapia. 2014;98:36–44.PubMedCrossRef Ogbourne SM, Parsons PG. The value of nature's natural product library for the discovery of new chemical entities: the discovery of ingenol mebutate. Fitoterapia. 2014;98:36–44.PubMedCrossRef
8.
go back to reference Noble RL. The discovery of the vinca alkaloids—chemotherapeutic agents against cancer. Biochem Cell Biol. 1990;68(12):1344–51.PubMedCrossRef Noble RL. The discovery of the vinca alkaloids—chemotherapeutic agents against cancer. Biochem Cell Biol. 1990;68(12):1344–51.PubMedCrossRef
9.
go back to reference Wall ME, Wani MC. Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996;51(1):239–54.PubMedCrossRef Wall ME, Wani MC. Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996;51(1):239–54.PubMedCrossRef
10.
go back to reference WHO. WHO traditional medicine strategy 2002–2005. 2002. WHO. WHO traditional medicine strategy 2002–2005. 2002.
11.
go back to reference Gbile Z, Adesina S. Nigerian flora and its pharmaceutical potential. J Ethnopharmacol. 1987;19(1):1–16.PubMedCrossRef Gbile Z, Adesina S. Nigerian flora and its pharmaceutical potential. J Ethnopharmacol. 1987;19(1):1–16.PubMedCrossRef
12.
go back to reference Ajaiyeoba E, Ashidi J, Abiodun O, Okpako L, Ogbole O, Akinboye D, Falade C, Bolaji O, Gbotosho G, Falade M. Antimalarial ethnobotany: in vitro. Antiplasmodial activity of seven plants identified in the Nigerian middle belt. Pharm Biol. 2005;42(8):588–91.CrossRef Ajaiyeoba E, Ashidi J, Abiodun O, Okpako L, Ogbole O, Akinboye D, Falade C, Bolaji O, Gbotosho G, Falade M. Antimalarial ethnobotany: in vitro. Antiplasmodial activity of seven plants identified in the Nigerian middle belt. Pharm Biol. 2005;42(8):588–91.CrossRef
13.
go back to reference Abubakar M, Musa A, Ahmed A, Hussaini I. The perception and practice of traditional medicine in the treatment of cancers and inflammations by the Hausa and Fulani tribes of northern Nigeria. J Ethnopharmacol. 2007;111(3):625–9.PubMedCrossRef Abubakar M, Musa A, Ahmed A, Hussaini I. The perception and practice of traditional medicine in the treatment of cancers and inflammations by the Hausa and Fulani tribes of northern Nigeria. J Ethnopharmacol. 2007;111(3):625–9.PubMedCrossRef
14.
go back to reference Soladoye MO, Amusa N, Raji-Esan S, Chukwuma E, Taiwo A. Ethnobotanical survey of anti-cancer plants in Ogun state, Nigeria. Annals. Biol Res. 2010;1(4):261–73. Soladoye MO, Amusa N, Raji-Esan S, Chukwuma E, Taiwo A. Ethnobotanical survey of anti-cancer plants in Ogun state, Nigeria. Annals. Biol Res. 2010;1(4):261–73.
15.
go back to reference Ngulde SI, Sandabe UK, Hussaini IM. Ethnobotanical survey of anticancer plants in Askira/Uba local government area of Borno state, Nigeria. Afr J Pharm Pharmacol. 2015;9(5):123–30.CrossRef Ngulde SI, Sandabe UK, Hussaini IM. Ethnobotanical survey of anticancer plants in Askira/Uba local government area of Borno state, Nigeria. Afr J Pharm Pharmacol. 2015;9(5):123–30.CrossRef
16.
go back to reference Ogbole OO, Adeniji JA, Ajaiyeoba EO. Cytotoxicity evaluation of sixteen Nigerian medicinal plant extracts using the human rhabdomyosarcoma cell line. Niger J Nat Prod Med. 2015;18(1):1–6. Ogbole OO, Adeniji JA, Ajaiyeoba EO. Cytotoxicity evaluation of sixteen Nigerian medicinal plant extracts using the human rhabdomyosarcoma cell line. Niger J Nat Prod Med. 2015;18(1):1–6.
17.
go back to reference Ashidi JS, Houghton PJ, Hylands PJ, Efferth T. Ethnobotanical survey and cytotoxicity testing of plants of South-western Nigeria used to treat cancer, with isolation of cytotoxic constituents from Cajanus cajan Millsp. Leaves. J Ethnopharmacol. 2010;128(2):501–12.PubMedCrossRef Ashidi JS, Houghton PJ, Hylands PJ, Efferth T. Ethnobotanical survey and cytotoxicity testing of plants of South-western Nigeria used to treat cancer, with isolation of cytotoxic constituents from Cajanus cajan Millsp. Leaves. J Ethnopharmacol. 2010;128(2):501–12.PubMedCrossRef
18.
go back to reference Mclaughlin JL. Crown gall tumours on potato discs and brine shrimp lethality: two simple bioassays for higher plant screening and fractionation. Methods in plant. Biochemistry. 1991;6:1–32. Mclaughlin JL. Crown gall tumours on potato discs and brine shrimp lethality: two simple bioassays for higher plant screening and fractionation. Methods in plant. Biochemistry. 1991;6:1–32.
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference Meyer B, Ferrigni N, Putnam J, Jacobsen L, Nichols DJ, McLaughlin JL. Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med. 1982;45(05):31–4.CrossRef Meyer B, Ferrigni N, Putnam J, Jacobsen L, Nichols DJ, McLaughlin JL. Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med. 1982;45(05):31–4.CrossRef
21.
go back to reference Ramachandran S, Vamsikrishna M, Gowthami K, Heera B, Dhanaraju M. Assessment of cytotoxic activity of Agave cantula using brine shrimp (Artemia salina) lethality bioassay. Asian J, Sci. Res. 2011;4(1):90–4. Ramachandran S, Vamsikrishna M, Gowthami K, Heera B, Dhanaraju M. Assessment of cytotoxic activity of Agave cantula using brine shrimp (Artemia salina) lethality bioassay. Asian J, Sci. Res. 2011;4(1):90–4.
22.
go back to reference Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, Minor L. Cell viability assays. 2016. Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, Minor L. Cell viability assays. 2016.
23.
go back to reference Gerlier D, Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods. 1986;94(1–2):57–63.PubMedCrossRef Gerlier D, Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods. 1986;94(1–2):57–63.PubMedCrossRef
24.
go back to reference Suffness M, Pezzuto JM. Assays related to cancer drug discovery. Methods in Plant Biochemistry: Assays for Bioactivity. 1990;6:71–133. Suffness M, Pezzuto JM. Assays related to cancer drug discovery. Methods in Plant Biochemistry: Assays for Bioactivity. 1990;6:71–133.
25.
go back to reference Wong YH, Abdul Kadir H, Ling SK: Bioassay-Guided Isolation of Cytotoxic Cycloartane Triterpenoid Glycosides from the Traditionally Used Medicinal Plant Leea indica. Evidence-based complementary and alternative medicine: eCAM. 2012;2012:164689. Wong YH, Abdul Kadir H, Ling SK: Bioassay-Guided Isolation of Cytotoxic Cycloartane Triterpenoid Glycosides from the Traditionally Used Medicinal Plant Leea indica. Evidence-based complementary and alternative medicine: eCAM. 2012;2012:164689.
26.
go back to reference Ondo J, Lekana-Douki J, Bongui J, Zang Edou E, Zatra R, Toure-Ndouo F, Elomri A, Lebibi J, Seguin E. Vitro antiplasmodial activity and cytotoxicity of extracts and fractions of Vitex madiensis, medicinal plant of Gabon. Tropical Med Int Health. 2012;17(3):316–21. Ondo J, Lekana-Douki J, Bongui J, Zang Edou E, Zatra R, Toure-Ndouo F, Elomri A, Lebibi J, Seguin E. Vitro antiplasmodial activity and cytotoxicity of extracts and fractions of Vitex madiensis, medicinal plant of Gabon. Tropical Med Int Health. 2012;17(3):316–21.
27.
go back to reference Ogbole OO, Ajaiyeoba EO, Adeniji JA, Kamdem SR, Sajan S, Muhammad IC. Bioassay-guided isolation of poliovirus-inhibiting constituents from Zephyranthes candida. Pharm Biol. 2015;53(6):882–7.CrossRef Ogbole OO, Ajaiyeoba EO, Adeniji JA, Kamdem SR, Sajan S, Muhammad IC. Bioassay-guided isolation of poliovirus-inhibiting constituents from Zephyranthes candida. Pharm Biol. 2015;53(6):882–7.CrossRef
28.
go back to reference Gbadamosi IT, Erinoso SMA. Review of twenty ethnobotanicals used in the management of breast cancer in Abeokuta, Ogun state, Nigeria. Afr J Pharm Pharmacol. 2016;10(27):546–64.CrossRef Gbadamosi IT, Erinoso SMA. Review of twenty ethnobotanicals used in the management of breast cancer in Abeokuta, Ogun state, Nigeria. Afr J Pharm Pharmacol. 2016;10(27):546–64.CrossRef
29.
go back to reference Soladoye M, Chukwuma E, Owa F. An ‘Avalanche’of plant species for the traditional cure of diabetes mellitus in south-western Nigeria. J Nat Prod Plant Resour. 2012;2(1):60–72. Soladoye M, Chukwuma E, Owa F. An ‘Avalanche’of plant species for the traditional cure of diabetes mellitus in south-western Nigeria. J Nat Prod Plant Resour. 2012;2(1):60–72.
30.
go back to reference Oliver-Bever B: Medicinal plants in tropical West Africa: Cambridge University press; 1986.CrossRef Oliver-Bever B: Medicinal plants in tropical West Africa: Cambridge University press; 1986.CrossRef
31.
go back to reference Adesegun S, Elechi N, Coker H. Antioxidant power of Macaranga barteri leaf. Am j Food Tech. 2007;2:543–9.CrossRef Adesegun S, Elechi N, Coker H. Antioxidant power of Macaranga barteri leaf. Am j Food Tech. 2007;2:543–9.CrossRef
32.
go back to reference Lee S-Y, Lee K-S, Yi SH, Kook S-H, Lee J-C. Acteoside suppresses RANKL-mediated Osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. PLoS One. 2013;8(12):e80873.PubMedPubMedCentralCrossRef Lee S-Y, Lee K-S, Yi SH, Kook S-H, Lee J-C. Acteoside suppresses RANKL-mediated Osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. PLoS One. 2013;8(12):e80873.PubMedPubMedCentralCrossRef
33.
go back to reference Lee K-W, Kim HJ, Lee YS, Park H-J, Choi J-W, Ha J, Lee K-T. Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G 0 /G 1 phase and differentiation into monocyte. Carcinogenesis. 2007;28(9):1928–36.PubMedCrossRef Lee K-W, Kim HJ, Lee YS, Park H-J, Choi J-W, Ha J, Lee K-T. Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G 0 /G 1 phase and differentiation into monocyte. Carcinogenesis. 2007;28(9):1928–36.PubMedCrossRef
34.
go back to reference Singh D, Sharma S, Rani R, Mishra S, Sharma R. Kaempferol-7-O-Glucoside and their antimicrobial screening isolate from Cassia renigera wall. Int. J. Pharm. Clin Res. 2011;3(2):30–4. Singh D, Sharma S, Rani R, Mishra S, Sharma R. Kaempferol-7-O-Glucoside and their antimicrobial screening isolate from Cassia renigera wall. Int. J. Pharm. Clin Res. 2011;3(2):30–4.
35.
go back to reference Süzgeç-Selçuk S, Birteksöz AS. Flavonoids of Helichrysum chasmolycicum and its antioxidant and antimicrobial activities. S Afr J Bot. 2011;77(1):170–4.CrossRef Süzgeç-Selçuk S, Birteksöz AS. Flavonoids of Helichrysum chasmolycicum and its antioxidant and antimicrobial activities. S Afr J Bot. 2011;77(1):170–4.CrossRef
36.
go back to reference Ohnishi M, Morishita H, Iwahashi H, Toda S, Shirataki Y, Kimura M, Kido R. Inhibitory effects of chlorogenic acids on linoleic acid peroxidation and haemolysis. Phytochemistry. 1994;36(3):579–83.CrossRef Ohnishi M, Morishita H, Iwahashi H, Toda S, Shirataki Y, Kimura M, Kido R. Inhibitory effects of chlorogenic acids on linoleic acid peroxidation and haemolysis. Phytochemistry. 1994;36(3):579–83.CrossRef
37.
go back to reference Reddy AV, Ravinder K, Narasimhulu M, Sridevi A, Satyanarayana N, Kondapi AK, Venkateswarlu Y. New anticancer bastadin alkaloids from the sponge Dendrilla cactos. Bioorg Med Chem. 2006;14(13):4452–7.PubMedCrossRef Reddy AV, Ravinder K, Narasimhulu M, Sridevi A, Satyanarayana N, Kondapi AK, Venkateswarlu Y. New anticancer bastadin alkaloids from the sponge Dendrilla cactos. Bioorg Med Chem. 2006;14(13):4452–7.PubMedCrossRef
38.
go back to reference Ngoumfo RM, Ngounou GE, Tchamadeu CV, Qadir MI, Mbazoa CD, Begum A, Ngninzeko FN, Lontsi D, Choudhary MI. Inhibitory effect of Macabarterin, a Polyoxygenated Ellagitannin from Macaranga barteri, on human Neutrophil respiratory burst activity. J Nat Prod. 2008;71(11):1906–10.PubMedCrossRef Ngoumfo RM, Ngounou GE, Tchamadeu CV, Qadir MI, Mbazoa CD, Begum A, Ngninzeko FN, Lontsi D, Choudhary MI. Inhibitory effect of Macabarterin, a Polyoxygenated Ellagitannin from Macaranga barteri, on human Neutrophil respiratory burst activity. J Nat Prod. 2008;71(11):1906–10.PubMedCrossRef
39.
go back to reference Burkill HM: The useful plants of west tropical Africa, Vols. 1–3: Royal Botanic Gardens, Kew; 1995. Burkill HM: The useful plants of west tropical Africa, Vols. 1–3: Royal Botanic Gardens, Kew; 1995.
40.
go back to reference Akah PA, Nwaiwu JI. Anticonvulsant activity of root and stem extracts of Calliandra portoricensis. J Ethnopharmacol. 1988;22(2):205–10.PubMedCrossRef Akah PA, Nwaiwu JI. Anticonvulsant activity of root and stem extracts of Calliandra portoricensis. J Ethnopharmacol. 1988;22(2):205–10.PubMedCrossRef
41.
go back to reference Adaramoye O, Erguen B, Oyebode O, Nitzsche B, Höpfner M, Jung K, Rabien A. Antioxidant, antiangiogenic and antiproliferative activities of root methanol extract of Calliandra portoricensis in human prostate cancer cells. J. Integr Med. 2015;13(3):185–93.CrossRef Adaramoye O, Erguen B, Oyebode O, Nitzsche B, Höpfner M, Jung K, Rabien A. Antioxidant, antiangiogenic and antiproliferative activities of root methanol extract of Calliandra portoricensis in human prostate cancer cells. J. Integr Med. 2015;13(3):185–93.CrossRef
42.
go back to reference Harwooda JS, Cutler HG, Jacyno JM. Nigrosporolide, a plant growth-inhibiting macrolide from the mould Nigrospora sphaerica. Nat Prod Lett. 1995;6(3):181–5.CrossRef Harwooda JS, Cutler HG, Jacyno JM. Nigrosporolide, a plant growth-inhibiting macrolide from the mould Nigrospora sphaerica. Nat Prod Lett. 1995;6(3):181–5.CrossRef
Metadata
Title
In vitro cytotoxic activity of medicinal plants from Nigeria ethnomedicine on Rhabdomyosarcoma cancer cell line and HPLC analysis of active extracts
Authors
Omonike O. Ogbole
Peter A. Segun
Adekunle J. Adeniji
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-2005-8

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue