Show simple item record

dc.contributor.author.Adem, Fozia A
dc.contributor.authorMbaveng, Armelle T.
dc.contributor.authorVictor, Kuete
dc.contributor.authorHeydenreich, Matthias
dc.contributor.authorAlbert, Ndakala
dc.contributor.authorBeatrice, Irungu
dc.contributor.authorAbiy, Yenesew
dc.contributor.authorThomas, Efferth
dc.date.accessioned2019-09-10T09:17:36Z
dc.date.available2019-09-10T09:17:36Z
dc.date.issued2019
dc.identifier.citationAdem, Fozia A., et al. "Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer." Phytomedicine 58 (2019): 152853.en_US
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0944711319300248
dc.identifier.urihttp://erepository.uonbi.ac.ke/handle/11295/107093
dc.description.abstractBackground While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells. Purpose The aim of this study was to determine the cytotoxicity of isoflavones: osajin (1), 5,7-dihydroxy-4ˈ-methoxy-6,8-diprenylisoflavone (2) and biflavonoids: chamaejasmin (3), 7,7″-di-O-methylchamaejasmin (4) and campylospermone A (5), a dimeric chromene [diphysin(6)] and an ester of ferullic acid with long alkyl chain [erythrinasinate (7)] isolated from the stem bark and roots of the Kenyan medicinal plant, Ormocarpum kirkii. The mode of action of compounds 2 and 4 was further investigated. Methods The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow cytometry was used to analyze the cell cycle (propodium iodide (PI) staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). CCRF-CEM leukemia cells were used as model cells for mechanistic studies. Results Compounds 1, 2 and 4 displayed IC50 values below 20 µM towards CCRF-CEM and CEM/ADR5000 leukemia cells, and were further tested towards a panel of 7 carcinoma cells. The IC50 values of the compounds against carcinoma cells varied from 16.90 µM (in resistant U87MG.ΔEGFR glioblastoma cells) to 48.67 µM (against HepG2 hepatocarcinoma cells) for 1, from 7.85 µM (in U87MG.ΔEGFR cells) to 14.44 µM (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 µM (towards U87MG.ΔEGFRcells) to 7.76 µM (against MDA-MB231/BCRP cells) for 4, and from 0.07 µM (against MDA-MB231 cells) to 2.15 µM (against HepG2 cells) for doxorubicin. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production. Conclusion The present report indicates that isoflavones and biflavonoids from Ormocarpum kirkii are cytotoxic compounds with the potential of being exploited in cancer chemotherapy. Compounds 2 and 4 deserve further studies to develop new anticancer drugs to fight sensitive and resistant cancer cell lines. Graphical abstract Compounds 2 and 4 displayed IC50 values below 20 µM towards CCRF-CEM and CEM/ADR5000 leukemia cells. Compounds 2 and 4 also showed the best cytotoxic effects against a panel of carcinoma cells with the IC50 values ranged from 7.85 µM (in U87MG.ΔEGFR cells) to 14.44 µM (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2 and from 4.96 µM (towards U87MG.ΔEGFRcells) to 7.76 µM (against MDA-MB231/BCRP cells) for 4. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production..................................................en_US
dc.language.isoenen_US
dc.publisherUniversity of Nairobien_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.titleCytotoxicity Of Isoflavones And Biflavonoids From Ormocarpum Kirkii Towards Multi-factorial Drug Resistant Canceren_US
dc.typeArticleen_US


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States