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.
Acknowledgment
E. Mfotie Njoya is very grateful to the University of Pretoria for the postdoctoral fellowship.
Competing interests: The authors declare that they have no competing interests.
Funding: This work was supported by the National Research Foundation (NRF), South Africa through the Incentive Funding for Rated Researchers (Lyndy J. McGaw).
References
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.Search in Google Scholar
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.10.3322/caac.21262Search in Google Scholar
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:E553.10.3390/molecules21050553Search in Google Scholar
4. Sen T, Samanta SK. Medicinal plants, human health and biodiversity: a broad review. Adv Biochem Eng/Biotechnol 2015;147:59–110.10.1007/10_2014_273Search in Google Scholar
5. Polhill RM, Wiens D. Flora of tropical East Africa. Rotterdam, the Netherlands: Balkema, AA, 1999.Search in Google Scholar
6. Kuijt J. The biology of parasitic flowering plants. Berkeley, CA: University of California Press, 1969.Search in Google Scholar
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.Search in Google Scholar
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;83:235–40.10.1016/S0378-8741(02)00244-1Search in Google Scholar
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.Search in Google Scholar
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.Search in Google Scholar
11. Balle S. Loranthacées. In: Satabié B, Leroy JF, editors. Flore du Cameroun, Vol. 23. Yaoundé, Cameroun, 1982:82.Search in Google Scholar
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;10:161–70.10.4314/ajtcam.v10i4.26Search in Google Scholar PubMed PubMed Central
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;98:945–52.10.1002/chin.201547208Search in Google Scholar
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.Search in Google Scholar
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;26:1775–81.10.1080/14786419.2011.603316Search in Google Scholar PubMed
16. Hasanean HA, Shanawany MAE, Bishay DW, Franz G. New triterpenoid glycosides from Taverniera aegyptiaca Boiss. Die Pharmazie 1992;47:143–7.Search in Google Scholar
17. Prolac A, Raynaud J. Isolation and identification of 8-C-galactosyl apigenine from leaves of Carlina ancathifolia. Helvetica Chimica Acta 1983;66:2412–3.10.1002/hlca.19830660804Search in Google Scholar
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;75:522–7.10.1055/s-0029-1185328Search in Google Scholar PubMed
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;7:15–27.10.2174/157488412799218815Search in Google Scholar PubMed
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;82:171–9.10.1055/s-0035-1557900Search in Google Scholar PubMed
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;25:270–4.10.1007/BF02976624Search in Google Scholar PubMed
22. Petronelli A, Pannitteri G, Testa U. Triterpenoids as new promising anticancer drugs. Anticancer Drugs 2009;20:880–92.10.1097/CAD.0b013e328330fd90Search in Google Scholar PubMed
23. Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev 2010;9:425–74.10.1007/s11101-010-9183-zSearch in Google Scholar PubMed PubMed Central
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.Search in Google Scholar
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:e0159430.10.1371/journal.pone.0159430Search in Google Scholar PubMed PubMed Central
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.Search in Google Scholar
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:e64278.10.1371/journal.pone.0064278Search in Google Scholar PubMed PubMed Central
28. Olsson M, Zhivotovsky B. Caspases and cancer. Cell Death Diff 2011;18:1441–9.10.1038/cdd.2011.30Search in Google Scholar PubMed PubMed Central
29. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997;326(Pt 1):1–16.10.1042/bj3260001Search in Google Scholar PubMed PubMed Central
30. Cryns V, Yuan J. Proteases to die for. Genes Dev 1998;12:1551–70.10.1101/gad.12.11.1551Search in Google Scholar PubMed
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;131:1445–54.10.1002/ijc.27365Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/znc-2019-0171).
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