Cytotoxicity of compounds from Xylopia aethiopica towards multi-factorial drug-resistant cancer cells

Introduction: Multidrug resistance (MDR) in cancer represent a major hurdle in chemotherapy. Previously, the methanol extract of the medicinal spice Xylopia aethiopica displayed considerable cytotoxicity against multidrug resistant (MDR) cancer cell lines. Methods: The present study was designed to assess the cytotoxicity of compounds, 16 alpha-hydroxy-entkauran-19-oic acid (2), 3,4',5-trihydroxy-6 '',6 ''-dimethylpyrano[2,3-g]flavone (3), isotetrandrine (5) and trans-tiliroside (6) derived from the methanol crude extract of Xylopia aethiopica against 9 drug-sensitive and -resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondria] membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry. Results: Flavonoid 3 and alkaloid 5 also displayed IC50 values ranging from 2.61 mu M (towards leukemia CCRF-CEM cells) to 18.60 mu M (towards gliobastoma multiforme U87MG.Delta EGFR cells) and from 1.45 mu M (towards HepG2 cells) to 7.28 mu M (towards MDA-MB-231-pcDNA cells), respectively. IC50 values ranged from 0.20 mu M (against CCRF-CEM cells) to 195.12 mu M (against CEM/ADR5000 cells) for doxorubicin. Compound 3 induced apoptosis in leukemia CCRF-CEM cells mediated by the disruption of the MMP, whilst 5 induced apoptosis mediated by ROS production. Conclusions: Compounds 2 and 5 represent potential cytotoxic phytochemicals that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug -resistant cancers. (C) 2015 Elsevier GmbH. All rights reserved.