Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells

Introduction: The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy. Methods: In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F (1, a flavanone) and poinsettifolin B (2, a chalcone) against 9 drug-sensitive and multidrug-resistant (MDR) 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 analysed via flow cytometry. Results: Compounds 1 and 2 displayed cytotoxic effects with IC50 values below 34 mu M in all the 9 tested cancer cell lines. The IC50 values for flavanone 1 and chalcone 2 ranged from 5.34 mu M and 1.94 mu M (towards leukaemia CCRF-CEM cells) to 33.30 mu M and 28.92 mu M (towards MDA-MB-231-BCRP cells), respectively, and from 0.20 mu M (against CCRF-CEM cells) to 195.12 mu M (against CEM/ADR5000 cells) for doxorubicin. The compounds induced apoptosis in CCRF-CEM leukaemia cells, mediated by MMP disruption and increased ROS production. Conclusions: Dorsmain F and poinsettifolin B are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. 0 2015 Elsevier GmbH. All rights reserved.