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Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells

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Summary

Introduction Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry. Results Anthraquinones 1 and 2 displayed cytotoxic effects with IC50 values below 81 μM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC50 values for compounds 1 and 2 ranged from 3.12 μM and 12.18 μM (towards leukemia CCRF-CEM cells) and from 30.32 μM and 80.11 μM (towards gliobastoma U87MG.ΔEGFR cells) respectively, and from 0.20 μM (against CCRF-CEM cells) to 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. Conclusions Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers.

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Acknowledgments

Authors acknowledge the Cameroon National Herbarium (Yaoundé) for the plant identification. VK is very grateful to the Alexander von Humboldt Foundation for an 18 months’ fellowship in Germany through the “Georg Foster Research Fellowship for Experienced Researcher” program. Authors also acknowledge the DAAD for a stipend to MZ.

Conflict of interest

The authors declare that they have no cnflict of interests.

Authors’ contribution

VK and MZ carried out the experiments; VK, ARND and PT contributed to plant’s collection, compound’s isolation and/or identification. VK wrote the manuscript. VK, PT and TE designed the experiments; TE supervised the work, provided the facilities for the study. All authors read the manuscript and approved the final version.

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Authors and Affiliations

  1. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany

    Victor Kuete, Maen Zeino & Thomas Efferth

  2. Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon

    Victor Kuete & Armelle T. Mbaveng

  3. Department of Organic Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon

    Arno R. Nanfack Donfack & Pierre Tane

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  1. Victor Kuete
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  5. Pierre Tane
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  6. Thomas Efferth
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Correspondence to Thomas Efferth.

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Kuete, V., Donfack, A.R.N., Mbaveng, A.T. et al. Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells. Invest New Drugs 33, 861–869 (2015). https://doi.org/10.1007/s10637-015-0268-9

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