Abstract
BackgroundCancer chemotherapy is still hampered by clinical failures due to multi-drug resistance (MDR) of tumor cells. In the present study, we have investigated the cytotoxicity of 20 methanol extracts from 10 medicinal plants against the sensitive leukemia CCRF-CEM cells. The most cytotoxic extracts were then further tested on a panel of 8 human cancer cell lines, including various MDR phenotypes.MethodsThe cytotoxicity of the 20 methanol extracts from 10 Cameroonian medicinal plants was determined using a resazurin reduction assay. Meanwhile, flow cytometry was used to measure cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS).ResultsIn the preliminary assay using CCRF-CEM cells, 12 extracts from five plants displayed IC50 values below 80 μg/mL, namely Albizia adianthifolia, Alchornea cordifolia, Alchornea laxiflora, Pennisetum purpureum, and Spathodea campanulata. the four best extracts were from two plants: Albizia adianthifolia roots (AAR) and bark (AAB) as well as Alchornea cordifolia leaves (ACL) and bark (ACB) had respective IC50 values of 0.98 μg/mL, 1.45 μg/mL, 8.02 μg/mL and 12.57 μg/mL in CCRF-CEM cells. They were further tested in 8 other cell lines as well as in normal AML12 hepatocytes. IC50 values ranging from 2.71 μg/mL (towards glioblastoma U87MG.ΔEGFR cells) to 10.30 μg/mL (towards breast adenocarcinoma MDA-MB-231-BCRP cells) for AAB, from 3.43 μg/mL (towards U87MG cells) to 10.77 μg/mL (towards colon carcinoma HCT116 (p53−/−) cells) for AAR and from 0.11 μg/mL (towards CCRF-CEM cells) to 108 μg/mL (towards leukemia CEM/ADR5000 cells) for doxorubicin (as control drug) were obtained. ACL and ACB extracts displayed selective activities. AAR and ACL extracts induced apoptosis in CCRF-CEM cells, through caspases activation and loss of MMP, while apoptotic cell death was mediated by MMP diruption and increase ROS production for ACL.ConclusionSome of the tested plants namely Albizia adianthifolia, Alchornea cordifolia, Alchornea laxiflora, Pennisetum purpureum, Spathodea campanulata represent a potential source of novel anticancer drugs. Especially, Albizia adianthifolia and Alchornea cordifolia revealed considerable cytotoxic activities that could be exploited to develop phytomedicines to fight cancers including MDR phenotypes.
Highlights
Cancer chemotherapy is still hampered by clinical failures due to multi-drug resistance (MDR) of tumor cells
Chemotherapy is still hampered by treatment failures due to multidrug resistance (MDR) of cancer cells
In the present investigation, the cytotoxicity of 20 methanol extracts from 10 plants was first determined at different concentrations in drug-sensitive CCRF-CEM leukemia cells
Summary
Cancer chemotherapy is still hampered by clinical failures due to multi-drug resistance (MDR) of tumor cells. Anticancer drug development should take into account the fact that cancer cells rapidly acquire resistance [2,3,4,5] Natural ressources such as medicinal plants constitute an indeniable reservoir of antiproliferative compounds [6]. Several bioactive compounds belonging to several classes of secondary metabolites isolated from African plants showed considerable antiproliferative activity against MDR cancer cells Some of these molecules include benzophenones (2,2′,5,6′-tetrahydroxybenzophenone, guttiferone E, isogarcinol and isoxanthochymo) [7], xanthones (xanthone V1, quinones: 2-acetylfuro-1,4-naphthoquinone) [8], flavonoids (gancaonin Q, 4-hydroxylonchocarpin, 6-prenylapigenin, 6,8-diprenyleriodictyol [9], 2′,4′-dihydroxy-3′,6′-dimethoxychalcone, 4′-hydroxy-2′,6′-dimethoxychalcone, cardamomin [10, 11], 8-hydroxycudraxanthone G, morusignin I and cudraxanthone I [12] and alkaloids (isotetrandrine [13], montrofoline, 1-hydroxy-4-methoxy-10-methylacridone, norevoxanthine, evoxanthine and 1,3-dimethoxy10-methylacridone) [14]. These plants include Echinops giganteus, Xylopia aethiopica, Piper capense, Imperata cylindrica [15, 16], Beilschmiedia acuta, Clausena anisata, Fagara tessmannii, Newbouldia laevis, Polyscias fulva [17], Garcina lucida, Fagara heitzii, Hymenocardia lyrata [18], Gladiolus quartinianus, Vepris soyauxii and Anonidium mannii [19]
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