Selective cytotoxic activity of isolated compounds from Globimetula dinklagei and Phragmanthera capitata (Loranthaceae)

Emmanuel Mfotie Njoyahttp://orcid.org/https://orcid.org/0000-0003-1163-7202 1 , 2 , Hermine L.D. Maza 3 , Pierre Mkounga 3 , Ulrich Koert 4 , Augustin E. Nkengfack 3  and Lyndy J. McGaw 1
  • 1 Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria 0110, South Africa
  • 2 Department of Biochemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • 3 Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • 4 Faculty of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, D-35043 Marburg, Germany
Emmanuel Mfotie NjoyaORCID iD: https://orcid.org/0000-0003-1163-7202
  • Corresponding author
  • Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria 0110, South Africa
  • Department of Biochemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • orcid.org/0000-0003-1163-7202
  • Email
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Hermine L.D. Maza
  • Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Pierre Mkounga
  • Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Ulrich Koert
  • Faculty of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, D-35043 Marburg, Germany
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Augustin E. Nkengfack
  • Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, PO Box 812, Yaoundé, Cameroon
  • Search for other articles:
  • degruyter.comGoogle Scholar
and Lyndy J. McGaw
  • Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria 0110, South Africa
  • Search for other articles:
  • degruyter.comGoogle Scholar

Abstract

This study aimed to evaluate the selective cytotoxicity of six natural compounds on four cancerous cells (MCF-7, HeLa, Caco-2 and A549) and two normal intestinal and lung cells (Hs1.Int and Wl-38) cells. We also attempted to analyze basically the structure–activity relationships and to understand the mechanism of action of active compounds using the Caspase-Glo® 3/7 kit. Globimetulin B (2) isolated from Globimetula dinklagei was significantly cytotoxic on cancerous cells with 50% inhibitory concentrations (IC50) ranging from 12.75 to 37.65 μM and the selectivity index (SI) values varying between 1.13 and 3.48 against both normal cells. The compound 3-O-β-d-glucopyranosyl-28-hydroxy-α-amyrin (5) isolated from Phragmanthera capitata exhibited the highest cytotoxic activity on HeLa cells with the IC50 of 6.88 μM and the SI of 5.20 and 8.71 against Hs1.Int and Wl-38 cells, respectively. A hydroxyl group at C-3 of compounds was suggested as playing an important role in the cytotoxic activity. The induction of caspase-3 and -7 activity represents some proof that apoptosis has occurred in treated cells. Globimetulin B (2) selectively killed cancer cells with less toxicity to non-cancerous cells as compared to conventional doxorubicin therapy.

  • 1.

    Stewart BW, Wild CP, editors. IARC/WHO: World Cancer Report 2014. International Agency for Research on Cancer/World Health Organization, Lyon, France, 2014. ISBN 978-92-832-0429-9.

  • 2.

    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Lai YJ, Tai CJ, Wang CW, Choong CY, Lee BH, Shi YC, et al. Anti-cancer activity of Solanum nigrum (AESN) through suppression of mitochondrial function and epithelial-mesenchymal transition (EMT) in breast cancer cells. Molecules 2016;21:E553.

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Sen T, Samanta SK. Medicinal plants, human health and biodiversity: a broad review. Adv Biochem Eng/Biotechnol 2015;147:59–110.

  • 5.

    Polhill RM, Wiens D. Flora of tropical East Africa. Rotterdam, the Netherlands: Balkema, AA, 1999.

  • 6.

    Kuijt J. The biology of parasitic flowering plants. Berkeley, CA: University of California Press, 1969.

  • 7.

    Calvin CL, Wilson CA. The haustorial system in African Loranthaceae. In: Polhill R, Wiens D, editors. The mistletoes of Africa. Kew, UK: Royal Botanic Gardens, 1998.

  • 8.

    Deeni YY, Sadiq NM. Antimicrobial properties and phytochemical constituents of the leaves of African mistletoe (Tapinanthus dodoneifolius (DC) Danser) (Loranthaceae): an ethnomedicinal plant of Hausaland, Northern Nigeria. J Ethnopharmacol 2002;83:235–40.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Dibong SD, Engone Obiang NL, Ndongo D, Priso RJ, Taffouo V, Fankem H, et al. An assessment on the uses of Loranthaceae in ethnopharmacology in Cameroon: a case study made in Logbessou, North of Douala. J Med Plants Res 2009;3:592–5.

  • 10.

    Dibong SD, Ndongo D, Priso RJ, Taffouo VD, Fankem H, Salle G, et al. Parasitism of host trees by the Loranthaceae in the region of Douala (Cameroon). Afr J Environ Sci Technol 2008;2:371–8.

  • 11.

    Balle S. Loranthacées. In: Satabié B, Leroy JF, editors. Flore du Cameroun, Vol. 23. Yaoundé, Cameroun, 1982:82.

  • 12.

    Adesina SK, Illoh HC, Johnny II, Jacobs IE. African mistletoes (Loranthaceae); ethnopharmacology, chemistry and medicinal values: an update. Afr J Tradit Complement Altern Med 2013;10:161–70.

    • PubMed
    • Export Citation
  • 13.

    Lenta BN, Ateba JT, Chouna JR, Aminake MN, Nardella F, Pradel G, et al. Two 2,6-dioxabicyclo[3.3.1]nonan-3-ones from Phragmanthera capitata (Spreng.) Balle (Loranthaceae). Helvetica Chimica Acta 2015;98:945–52.

    • Crossref
    • Export Citation
  • 14.

    Mkounga P, Maza HL, Ouahouo BM, Tyon LN, Hayato I, Hiroshi N, et al. New lupan-type triterpenoid derivatives from Globimetula dinklagei (Loranthaceae) hemiparasitic plant growing on Manihot esculenta (Euphorbiaceae). Z Nat Forsch 2016;71:381–6.

  • 15.

    Omeje EO, Osadebe PO, Esimone CO, Nworu CS, Kawamura A, Proksch P. Three hydroxylated lupeol-based triterpenoid esters isolated from the Eastern Nigeria mistletoe parasitic on Kola acuminata. Nat Prod Res 2012;26:1775–81.

    • Crossref
    • PubMed
    • Export Citation
  • 16.

    Hasanean HA, Shanawany MAE, Bishay DW, Franz G. New triterpenoid glycosides from Taverniera aegyptiaca Boiss. Die Pharmazie 1992;47:143–7.

  • 17.

    Prolac A, Raynaud J. Isolation and identification of 8-C-galactosyl apigenine from leaves of Carlina ancathifolia. Helvetica Chimica Acta 1983;66:2412–3.

    • Crossref
    • Export Citation
  • 18.

    Tabopda TK, Ngoupayo J, Khan Tanoli SA, Mitaine-Offer AC, Ngadjui BT, Ali MS, et al. Antimicrobial pentacyclic triterpenoids from Terminalia superba. Planta Med 2009;75:522–7.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Hasdenteufel F, Luyasu S, Hougardy N, Fisher M, Boisbrun M, Mertes PM, et al. Structure-activity relationships and drug allergy. Curr Clin Pharmacol 2012;7:15–27.

    • Crossref
    • PubMed
    • Export Citation
  • 20.

    Gao Y, He C, Bi W, Wu G, Altman E. Bioassay guided fractionation identified hederagenin as a major cytotoxic agent from Cyclocarya paliurus leaves. Planta Med 2016;82:171–9.

    • PubMed
    • Export Citation
  • 21.

    Tapondjou LA, Lontsi D, Sondengam BL, Choudhary MI, Park HJ, Choi J, et al. Structure-activity relationship of triterpenoids isolated from Mitragyna stipulosa on cytotoxicity. Arch Pharm Res 2002;25:270–4.

    • Crossref
    • PubMed
    • Export Citation
  • 22.

    Petronelli A, Pannitteri G, Testa U. Triterpenoids as new promising anticancer drugs. Anticancer Drugs 2009;20:880–92.

    • Crossref
    • PubMed
    • Export Citation
  • 23.

    Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev 2010;9:425–74.

    • Crossref
    • PubMed
    • Export Citation
  • 24.

    Salama MM, Kandil ZA, Islam WT. Cytotoxic compounds from the leaves of Gaillardia aristata Pursh growing in Egypt. Nat Prod Res 2012;26:2057–62.

    • PubMed
    • Export Citation
  • 25.

    Mishra T, Arya RK, Meena S, Joshi P, Pal M, Meena B, et al. Isolation, characterization and anticancer potential of cytotoxic triterpenes from Betula utilis bark. PLoS One 2016;11:e0159430.

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    Musa MA, Badisa VL, Latinwo LM, Cooperwood J, Sinclair A, Abdullah A. Cytotoxic activity of new acetoxycoumarin derivatives in cancer cell lines. Anticancer Res 2011;31:2017–22.

    • PubMed
    • Export Citation
  • 27.

    Ulukaya E, Frame FM, Cevatemre B, Pellacani D, Walker H, Mann VM, et al. Differential cytotoxic activity of a novel palladium-based compound on prostate cell lines, primary prostate epithelial cells and prostate stem cells. PLoS One 2013;8:e64278.

    • Crossref
    • PubMed
    • Export Citation
  • 28.

    Olsson M, Zhivotovsky B. Caspases and cancer. Cell Death Diff 2011;18:1441–9.

    • Crossref
    • Export Citation
  • 29.

    Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997;326(Pt 1):1–16.

  • 30.

    Cryns V, Yuan J. Proteases to die for. Genes Dev 1998;12:1551–70.

  • 31.

    Feng C, Zhou LY, Yu T, Xu G, Tian HL, Xu JJ, et al. A new anticancer compound, oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through Bax activation. Int J Cancer 2012;131:1445–54.

    • Crossref
    • PubMed
    • Export Citation
Purchase article
Get instant unlimited access to the article.
$42.00
Log in
Already have access? Please log in.


or
Log in with your institution

Journal + Issues

A Journal of Biosciences: Zeitschrift für Naturforschung C (ZNC) is an international scientific journal for the emerging field of natural and natural-like products. ZNC publishes original research on the isolation, bio-chemical synthesis and bioactivities of natural products, their biochemistry, pharmacology, biotechnology, and biological activity and innovative developed computational methods for predicting their structure and/or function.

Search