Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea 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 Dichrostachys cinerea, namely, betulinic acid (1), glyceryl-1-hexacosanoate (2), 7-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (3), and 6-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (4), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound 1. 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 1 and flavone 4 had cytotoxic effects towards the 9 tested cancer cell lines with IC50 values below 50 μM. The recorded IC50 values varied from 7.65 μM (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 μM (against HepG2 hepatocarcinoma cells) for 1, 18.90 μM (CCRF-CEM leukemia cells) to 88.86 μM (against HCT116p53