Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells
The effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of Dichrostachys cinerea, namely, betulinic acid (1), glyceryl-1-hexacosanoate (2),...
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doaj-fe11e05362574061a0d300fa45b5cd232020-11-25T02:13:38ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882019-01-01201910.1155/2019/84501588450158Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer CellsArmelle T. Mbaveng0Francois Damen1James D. Simo Mpetga2Maurice D. Awouafack3Pierre Tane4Victor Kuete5Thomas Efferth6Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, GermanyDepartment of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, CameroonDepartment of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, CameroonDepartment of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, CameroonDepartment of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, CameroonDepartment of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, GermanyDepartment of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, GermanyThe effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of Dichrostachys cinerea, namely, betulinic acid (1), glyceryl-1-hexacosanoate (2), 7-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (3), and 6-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (4), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound 1. The resazurin reduction assay was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed by flow cytometry. Constituents of DCB were isolated by column chromatography. Triterpenoid 1 and flavone 4 had cytotoxic effects towards the 9 tested cancer cell lines with IC50 values below 50 μM. The recorded IC50 values varied from 7.65 μM (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 μM (against HepG2 hepatocarcinoma cells) for 1, 18.90 μM (CCRF-CEM leukemia cells) to 88.86 μM (against HCT116p53+/+ colon adenocarcinoma cells) for 4, and 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. DCB induced apoptosis in CCRF-CEM cells mostly mediated by MMP alteration and enhanced ROS production; compound 1 induced apoptosis through caspases activation and MMP alteration and increased ROS production. Dichrostachys cinerea is an interesting cytotoxic plant and deserves more studies leading to new antineoplastic agents to fight cancer and mostly leukemia.http://dx.doi.org/10.1155/2019/8450158 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Armelle T. Mbaveng Francois Damen James D. Simo Mpetga Maurice D. Awouafack Pierre Tane Victor Kuete Thomas Efferth |
spellingShingle |
Armelle T. Mbaveng Francois Damen James D. Simo Mpetga Maurice D. Awouafack Pierre Tane Victor Kuete Thomas Efferth Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells Evidence-Based Complementary and Alternative Medicine |
author_facet |
Armelle T. Mbaveng Francois Damen James D. Simo Mpetga Maurice D. Awouafack Pierre Tane Victor Kuete Thomas Efferth |
author_sort |
Armelle T. Mbaveng |
title |
Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells |
title_short |
Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells |
title_full |
Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells |
title_fullStr |
Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells |
title_full_unstemmed |
Cytotoxicity of Crude Extract and Isolated Constituents of the Dichrostachys cinerea Bark towards Multifactorial Drug-Resistant Cancer Cells |
title_sort |
cytotoxicity of crude extract and isolated constituents of the dichrostachys cinerea bark towards multifactorial drug-resistant cancer cells |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2019-01-01 |
description |
The effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of Dichrostachys cinerea, namely, betulinic acid (1), glyceryl-1-hexacosanoate (2), 7-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (3), and 6-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (4), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound 1. The resazurin reduction assay was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed by flow cytometry. Constituents of DCB were isolated by column chromatography. Triterpenoid 1 and flavone 4 had cytotoxic effects towards the 9 tested cancer cell lines with IC50 values below 50 μM. The recorded IC50 values varied from 7.65 μM (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 μM (against HepG2 hepatocarcinoma cells) for 1, 18.90 μM (CCRF-CEM leukemia cells) to 88.86 μM (against HCT116p53+/+ colon adenocarcinoma cells) for 4, and 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. DCB induced apoptosis in CCRF-CEM cells mostly mediated by MMP alteration and enhanced ROS production; compound 1 induced apoptosis through caspases activation and MMP alteration and increased ROS production. Dichrostachys cinerea is an interesting cytotoxic plant and deserves more studies leading to new antineoplastic agents to fight cancer and mostly leukemia. |
url |
http://dx.doi.org/10.1155/2019/8450158 |
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