Cytotoxicity and Modes of Action of the Methanol Extracts of Six Cameroonian Medicinal Plants against Multidrug-Resistant Tumor Cells

Abstract

Introduction. The present study aims at evaluating the cytotoxicity of twelve parts from six Cameroonian medicinal plants on sensitive and drug-resistant cancer cell lines. We also studied the mode of action of the most active plants,Gladiolus quartinianus,Vepris soyauxii, andAnonidium mannii.Methods. The cytotoxicity of the extracts was determined using a resazurin assay. Flow cytometry was used for cell-cycle analysis and detection of apoptosis, analysis of mitochondrial membrane potential (MMP), and measurement of reactive oxygen species (ROS).Results. At 40 g/mL, three extracts showed a growth of CCRF-CEM leukemia cells by less than 50%. This includes the extracts fromG. quartinianus(GQW; 25.69%),Vepris soyauxiileaves (VSL; 29.82%), andAnonidium manniileaves (AML; 31.58%). The lowest IC₅₀values below 30 μg/mL were obtained with GQW, AML and VSL against 7/9, 8/9, and 9/9 tested cancer cell lines, respectively. The lowest IC₅₀values for each plant were 4.09 μg/mL, and 9.14 μg/mL (against U87MG.ΔEGFRcells), respectively, for VSL and AML and 10.57 μg/mL (against CCRF-CEM cells) for GQW. GQW induced cell cycle arrest between G0/G1 and S phases, whilst VSL and AML induced arrest in G0/G1. All three extracts induced apoptosis in CCRF-CEM cells by loss of MMP, whilst AML also enhanced production of ROS.Conclusion. The three active plants may be a source for the development of new anticancer drugs.