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

Victor Kuete; Armelle T Mbaveng; Maen Zeino; Bathelemy Ngameni; Gilbert Deccaux W F Kapche; Simeon F Kouam; Bonaventure T Ngadjui; Thomas Efferth

doi:10.1016/j.phymed.2015.04.007

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

Phytomedicine. 2015 Jul 15;22(7-8):737-43. doi: 10.1016/j.phymed.2015.04.007. Epub 2015 May 22.

Authors

Victor Kuete¹, Armelle T Mbaveng², Maen Zeino³, Bathelemy Ngameni⁴, Gilbert Deccaux W F Kapche⁵, Simeon F Kouam⁵, Bonaventure T Ngadjui⁶, Thomas Efferth⁷

Affiliations

¹ Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany ; Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
² Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
³ Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
⁴ Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
⁵ Department of Chemistry, Higher Teachers' Training College, University of Yaoundé I, Yaoundé, Cameroon.
⁶ Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
⁷ Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany . Electronic address: [email protected].

PMID: 26141760
DOI: 10.1016/j.phymed.2015.04.007

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.

Keywords: Apoptosis; Cytotoxicity; Dorsmanin F; Flavonoids; Multi-drug resistance; Poinsettifolin B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Caspases / metabolism
Cell Cycle / drug effects
Cell Line, Tumor / drug effects
Chalcones / pharmacology*
Drug Resistance, Multiple*
Drug Resistance, Neoplasm*
Flavonoids / pharmacology*
Humans
Inhibitory Concentration 50
Membrane Potential, Mitochondrial / drug effects
Molecular Structure
Reactive Oxygen Species / metabolism

Substances

Antineoplastic Agents, Phytogenic
Chalcones
Flavonoids
Reactive Oxygen Species
dorsmanin F
poinsettifolin B
Caspases