TY  - JOUR
A1  - Adem, Fozia A.
A1  - Mbaveng, Armelle T.
A1  - Kuete, Victor
A1  - Heydenreich, Matthias
A1  - Ndakala, Albert
A1  - Irungu, Beatrice
A1  - Yenesew, Abiy
A1  - Efferth, Thomas
T1  - Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer
JF  - Phytomedicine : international journal of phytotherapy and phytopharmacology
N2  - Background: 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. 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 mu M 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 mu M (in resistant U87MG.Delta EGFR glioblastoma cells) to 48.67 mu M (against HepG2 hepatocarcinoma cells) for 1, from 7.85 mu M (in U87MG.Delta EGFR cells) to 14.44 mu M (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 mu M (towards U87MG.Delta EGFRcells) to 7.76 mu M (against MDA-MB231/BCRP cells) for 4, and from 0.07 mu M (against MDA-MB231 cells) to 2.15 mu M (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.
KW  - Apoptosis
KW  - Cancer
KW  - Ormocarpum kirkii
KW  - Isoflavone
KW  - Biflavonoid
KW  - Multi-drug resistance
Y1  - 2019
U6  - https://doi.org/10.1016/j.phymed.2019.152853
SN  - 0944-7113
SN  - 1618-095X
VL  - 58
PB  - Elsevier
CY  - München
ER  -