Cytotoxicity of Crude Extract and Isolated Constituents of the Bark towards Multifactorial Drug-Resistant Cancer Cells.

The effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of namely, betulinic acid (), glyceryl-1-hexacosanoate (), 7-hydroxy-2-(4-hydroxyphenyl)-4-chromen-4-one (), and 6-hydroxy-2-(4-hydroxyphenyl)-4-chromen-4-one (), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound . The resazurin reduction assay was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed by flow cytometry. Constituents of DCB were isolated by column chromatography. Triterpenoid and flavone had cytotoxic effects towards the 9 tested cancer cell lines with IC values below 50 M. The recorded IC values varied from 7.65 M (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 M (against HepG2 hepatocarcinoma cells) for , 18.90 M (CCRF-CEM leukemia cells) to 88.86 M (against HCT116p53 colon adenocarcinoma cells) for and 0.02 M (against CCRF-CEM cells) to 122.96 M (against CEM/ADR5000 cells) for doxorubicin. DCB induced apoptosis in CCRF-CEM cells mostly mediated by MMP alteration and enhanced ROS production; compound induced apoptosis through caspases activation and MMP alteration and increased ROS production. is an interesting cytotoxic plant and deserves more studies leading to new antineoplastic agents to fight cancer and mostly leukemia.