Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

Introduction Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal ( 1), damnacanthol ( 2), 3-hydroxy-2-hydroxymethyl anthraquinone ( 3) and schimperiquinone B ( 4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry. Results Anthraquinones 1 and 2 displayed cytotoxic effects with IC values below 81 μM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC values for compounds 1 and 2 ranged from 3.12 μM and 12.18 μM (towards leukemia CCRF-CEM cells) and from 30.32 μM and 80.11 μM (towards gliobastoma U87MG.Δ EGFR cells) respectively, and from 0.20 μM (against CCRF-CEM cells) to 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. Conclusions Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers. [ABSTRACT FROM AUTHOR]