Victor Kuete1, Armelle T Mbaveng2, Maen Zeino3, Christian D Fozing4, Bathelemy Ngameni5, Gilbert Deccaux W F Kapche6, Bonaventure T Ngadjui4, Thomas Efferth7. 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 Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. 5. Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon. 6. Department of Chemistry, Higher Teachers' Training College, 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: efferth@uni-mainz.de.
Abstract
INTRODUCTION: Cancer remains an aggressive deadly disease, if drug resistance develops. This problem is aggravated by the fact that multiple rather than single mechanisms are involved in resistance and that multidrug resistance (MDR) phenomena cause inefficacy of many clinical established anticancer drugs. We are seeking for novel cytotoxic phytochemicals to combat drug-resistant tumour cells. METHODS: In the present study, we investigated the cytotoxicity of three naturally occurring flavonoids including two flavones artocarpesin (1) and cycloartocarpesin (2) and one chalcone, isobavachalcone (3) against 9 drug-sensitive and 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: Flavones 1 and 2 as well as chalcone 3 displayed cytotoxic effects at various extent on all the 9 tested cancer cell lines with IC50 values respectively below 106 µM, 50 µM and 25 µM. The IC50 values for the three investigational flavonoids ranged from 23.95 µM (towards hepatocarcinoma HepG2 cells) to 105 µM [towards colon carcinoma HCT116 (p53(-/-)) cells] for 1, from 15.51 µM (towards leukemia CCRF-CEM cells) to 49.83 µM [towards glioblastoma U87MG.ΔEGFR cells] for 2 and from 2.30 µM (towards CCRF-CEM cells) to 23.80 µM [towards colon carcinoma HCT116 (p53(+/+)) cells] for 3 and from 0.20 µM (towards CCRF-CEM cells) to 195.12 µM (towards leukemia CEM/ADR5000 cells) for doxorubicin. Compounds 2 and 3 induced apoptosis in CCRF-CEM leukemia cells, mediated by caspase activation and the disruption of MMP. CONCLUSIONS: The three tested flavonoids and mostly chalcone 3 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. Crown
INTRODUCTION:Cancer remains an aggressive deadly disease, if drug resistance develops. This problem is aggravated by the fact that multiple rather than single mechanisms are involved in resistance and that multidrug resistance (MDR) phenomena cause inefficacy of many clinical established anticancer drugs. We are seeking for novel cytotoxic phytochemicals to combat drug-resistant tumour cells. METHODS: In the present study, we investigated the cytotoxicity of three naturally occurring flavonoids including two flavonesartocarpesin (1) and cycloartocarpesin (2) and one chalcone, isobavachalcone (3) against 9 drug-sensitive and 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:Flavones 1 and 2 as well as chalcone 3 displayed cytotoxic effects at various extent on all the 9 tested cancer cell lines with IC50 values respectively below 106 µM, 50 µM and 25 µM. The IC50 values for the three investigational flavonoids ranged from 23.95 µM (towards hepatocarcinoma HepG2 cells) to 105 µM [towards colon carcinoma HCT116 (p53(-/-)) cells] for 1, from 15.51 µM (towards leukemia CCRF-CEM cells) to 49.83 µM [towards glioblastoma U87MG.ΔEGFR cells] for 2 and from 2.30 µM (towards CCRF-CEM cells) to 23.80 µM [towards colon carcinoma HCT116 (p53(+/+)) cells] for 3 and from 0.20 µM (towards CCRF-CEM cells) to 195.12 µM (towards leukemia CEM/ADR5000 cells) for doxorubicin. Compounds 2 and 3 induced apoptosis in CCRF-CEM leukemia cells, mediated by caspase activation and the disruption of MMP. CONCLUSIONS: The three tested flavonoids and mostly chalcone 3 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. Crown
Authors: Victor Kuete; Cedric F Tchinda; Flora T Mambe; Veronique P Beng; Thomas Efferth Journal: BMC Complement Altern Med Date: 2016-08-02 Impact factor: 3.659
Authors: Victor Kuete; Dominique Ngnintedo; Ghislain W Fotso; Oğuzhan Karaosmanoğlu; Bonaventure T Ngadjui; Felix Keumedjio; Samuel O Yeboah; Kerstin Andrae-Marobela; Hülya Sivas Journal: BMC Complement Altern Med Date: 2018-01-30 Impact factor: 3.659
Authors: Leticia Ribeiro de Assis; Reinaldo Dos Santos Theodoro; Maria Beatriz Silva Costa; Julyanna Andrade Silva Nascentes; Miguel Divino da Rocha; Meliza Arantes de Souza Bessa; Ralciane de Paula Menezes; Guilherme Dilarri; Giovane Böerner Hypolito; Vanessa Rodrigues Dos Santos; Cristiane Duque; Henrique Ferreira; Carlos Henrique Gomes Martins; Luis Octavio Regasini Journal: Membranes (Basel) Date: 2022-02-25