6533b85bfe1ef96bd12ba2ba

RESEARCH PRODUCT

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

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Abstract 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 IC 50 values below 34 µM in all the 9 tested cancer cell lines. The IC 50 values for flavanone 1 and chalcone 2 ranged from 5.34 µM and 1.94 µM (towards leukaemia CCRF-CEM cells) to 33.30 µM and 28.92 µM (towards MDA-MB-231- BCRP cells), respectively, and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (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.