Cytotoxic Compounds from the Fruits of Uapaca togoensis towards Multifactorial Drug-Resistant Cancer Cells

Autoren

Victor Kuete
Louis Sandjo
Jackson Seukep
Maen Zeino
Armelle Mbaveng
Bonaventure Ngadjui
Thomas Efferth

DOI

10.1055/s-0034-1383362

eISSN

1439-0221

ISSN

0032-0943

Ausgabe der Veröffentlichung

01

Zeitschrift

Planta Medica

Sprache

en

Online publication date

2014

Paginierung

32 - 38

Status

Published online

Herausgeber

Georg Thieme Verlag KG

Herausgeber URL

http://dx.doi.org/10.1055/s-0034-1383362

Datum der Datenerfassung

2017

Titel

Cytotoxic Compounds from the Fruits of Uapaca togoensis towards Multifactorial Drug-Resistant Cancer Cells

Ausgabe der Zeitschrift

81

Data source: Crossref

Abstract

Cancer cells may rapidly acquire multidrug resistance, mainly due to the presence of adenosine triphosphate-binding cassette transporters, epidermal growth factor receptor, or mutations in the p53 tumor suppressor gene. This work was designed to assess the cytotoxicity of the methanol crude extracts and compounds from the fruits of Uapaca togoensis, namely, β-amyryl acetate (1), 11-oxo-α-amyryl acetate (2), lupeol (3), pomolic acid (4), futokadsurin B (5), arborinin (6), and 3-O-β-D-glucopyranosyl sitosterol (7) against nine drug sensitive and multidrug-resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of the fruits of U. togoensis and compounds, whilst the caspase-Glo assay was used to detect the activation of caspase enzymes by the fruits of U. togoensis and compound 6. Cell cycle, mitochondrial membrane potential, and levels of reactive oxygen species were all analyzed via flow cytometry. The acridone alkoid 6 and the crude extract from the fruits of U. togoensis were active on all of the nine tested cancer lines with IC50 values below 32 µM and 30 µg/mL, respectively. Compounds 2 and 5 showed selective activities and IC50 values below 99 µM or 42 µM, respectively, which were obtained towards 3/9 and 6/9 tested cancer cell lines. Compound 6 displayed IC50 values below 10 µM towards seven of the nine tested cancer cell lines. The IC50 values ranged from 3.55 µM (against CEM/ADR5000 cells) to 31.77 µM (against CCRF-CEM cells) for alkaloid 6 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. The crude extract of the fruits of U. togoensis induced apoptosis in the CCRF-CEM leukemia cells, which was mediated by the disruption of the mitochondrial membrane potential. Compound 6 also strongly induced apoptosis in CCRF-CEM cells and cell cycle arrest in the G0/G1 and S phases. The crude extract from the fruits of this plant as well as aborinin are potential antiproliferative natural products that deserve further investigation to develop novel cytotoxic drugs to fight sensitive and otherwise drug-resistant phenotypes.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.

Autoren

Victor Kuete
Louis P Sandjo
Jackson A Seukep
Maen Zeino
Armelle T Mbaveng
Bonaventure Ngadjui
Thomas Efferth
Thomas Efferth

DOI

10.1055/s-0034-1383362

eISSN

1439-0221

Externe Identifier

PubMed Identifier: 25473921

Open access

false

ISSN

0032-0943

Ausgabe der Veröffentlichung

1

Zeitschrift

Planta medica

Schlüsselwörter

Cell Line, Tumor
Humans
Euphorbiaceae
Reactive Oxygen Species
Lignans
Triterpenes
Oleanolic Acid
Acridines
Doxorubicin
Plant Extracts
Antineoplastic Agents, Phytogenic
Drug Screening Assays, Antitumor
Inhibitory Concentration 50
Drug Resistance, Multiple
Molecular Structure
Drug Resistance, Neoplasm
Membrane Potential, Mitochondrial
Pentacyclic Triterpenes

Sprache

eng

Medium

Print-Electronic

Online publication date

2014

Paginierung

32 - 38

Datum der Veröffentlichung

2015

Status

Published

Datum der Datenerfassung

2014

Titel

Cytotoxic compounds from the fruits of Uapaca togoensis towards multifactorial drug-resistant cancer cells.

Sub types

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

Ausgabe der Zeitschrift

81

Data source: Europe PubMed Central

Abstract

Cancer cells may rapidly acquire multidrug resistance, mainly due to the presence of adenosine triphosphate-binding cassette transporters, epidermal growth factor receptor, or mutations in the p53 tumor suppressor gene. This work was designed to assess the cytotoxicity of the methanol crude extracts and compounds from the fruits of Uapaca togoensis, namely, β-amyryl acetate (1), 11-oxo-α-amyryl acetate (2), lupeol (3), pomolic acid (4), futokadsurin B (5), arborinin (6), and 3-O-β-D-glucopyranosyl sitosterol (7) against nine drug sensitive and multidrug-resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of the fruits of U. togoensis and compounds, whilst the caspase-Glo assay was used to detect the activation of caspase enzymes by the fruits of U. togoensis and compound 6. Cell cycle, mitochondrial membrane potential, and levels of reactive oxygen species were all analyzed via flow cytometry. The acridone alkoid 6 and the crude extract from the fruits of U. togoensis were active on all of the nine tested cancer lines with IC50 values below 32 µM and 30 µg/mL, respectively. Compounds 2 and 5 showed selective activities and IC50 values below 99 µM or 42 µM, respectively, which were obtained towards 3/9 and 6/9 tested cancer cell lines. Compound 6 displayed IC50 values below 10 µM towards seven of the nine tested cancer cell lines. The IC50 values ranged from 3.55 µM (against CEM/ADR5000 cells) to 31.77 µM (against CCRF-CEM cells) for alkaloid 6 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. The crude extract of the fruits of U. togoensis induced apoptosis in the CCRF-CEM leukemia cells, which was mediated by the disruption of the mitochondrial membrane potential. Compound 6 also strongly induced apoptosis in CCRF-CEM cells and cell cycle arrest in the G0/G1 and S phases. The crude extract from the fruits of this plant as well as aborinin are potential antiproliferative natural products that deserve further investigation to develop novel cytotoxic drugs to fight sensitive and otherwise drug-resistant phenotypes.

Autoren

Victor Kuete
Louis P Sandjo
Jackson A Seukep
Maen Zeino
Armelle T Mbaveng
Bonaventure Ngadjui
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/25473921

DOI

10.1055/s-0034-1383362

eISSN

1439-0221

Ausgabe der Veröffentlichung

1

Zeitschrift

Planta Med

Schlüsselwörter

Acridines
Antineoplastic Agents, Phytogenic
Cell Line, Tumor
Doxorubicin
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Euphorbiaceae
Humans
Inhibitory Concentration 50
Lignans
Membrane Potential, Mitochondrial
Molecular Structure
Oleanolic Acid
Pentacyclic Triterpenes
Plant Extracts
Reactive Oxygen Species
Triterpenes

Sprache

eng

Country

Germany

Paginierung

32 - 38

Datum der Veröffentlichung

2015

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2015

Titel

Cytotoxic compounds from the fruits of Uapaca togoensis towards multifactorial drug-resistant cancer cells.

Sub types

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

Ausgabe der Zeitschrift

81

Data source: PubMed

Cytotoxic Compounds from the Fruits of Uapaca togoensis towards Multifactorial Drug-Resistant Cancer Cells

Tools