6533b7d8fe1ef96bd126a5d7

RESEARCH PRODUCT

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

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Abstract 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 α -hydroxy- ent -kauran-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, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry. Results Flavonoid 3 and alkaloid 5 also displayed IC 50 values ranging from 2.61 µM (towards leukemia CCRF-CEM cells) to 18.60 µM (towards gliobastoma multiforme U87MG.Δ EGFR cells) and from 1.45 µM (towards HepG2 cells) to 7.28 µM (towards MDA-MB-231- pcDNA cells), respectively. IC 50 values ranged from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (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.