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  • Title: Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells.
    Author: Kuete V, Mbaveng AT, Zeino M, Ngameni B, Kapche GD, Kouam SF, Ngadjui BT, Efferth T.
    Journal: Phytomedicine; 2015 Jul 15; 22(7-8):737-43. PubMed ID: 26141760.
    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 IC50 values below 34 µM in all the 9 tested cancer cell lines. The IC50 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.
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