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Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines.
Phytomedicine. 2014 Oct 15; 21(12):1651-7.P

Abstract

INTRODUCTION

Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4'-hydroxy-2',6'-dimethoxychalcone (1), cardamomin (2), 2',4'-dihydroxy-3',6'-dimethoxychalcone (3)], and four flavanones [(S)-(-)-pinostrobin (4), (S)-(-)-onysilin (5) and alpinetin (6)] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types.

METHODS

The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometry for the mechanistic studies of the most active molecule (1).

RESULTS

IC50 values in a range of 2.54 μM against CEM/ADR5000 leukemia cells to 58.63 μM toward hepatocarcinoma HepG2 cells were obtained with 1. The lowest IC50 values of 8.59 μM for 2 and 10.67 μM for 3 were found against CCRF-CEM cells leukemia cells, whilst the corresponding values were above 80 μM for 4 and 6. P-glycoprotein-expressing and multidrug-resistant CEM/ADR5000 cells were much more sensitive toward compound 1 than toward doxorubicin and low cross-resistance or even collateral sensitivity was observed in other drug-resistent cell lines to this compound. Normal liver AML12 cells were more resistant to the studied compounds than HepG2 liver cancer cells, indicating tumor specificity at least to some extent. Compound 1 arrested the cell cycle between Go/G1 phase, strongly induced apoptosis via disrupted mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in the studied leukemia cell line.

CONCLUSIONS

Chalcone 1 was the best tested cytotoxic molecule and further studies will be performed in order to envisage its possible use in the fight against multifactorial resistant cancer cells.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Kuete V
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, P.O. Box 67, Dschang, Cameroon.
Nkuete AH
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Mbaveng AT
Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Wiench B
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
Wabo HK
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Tane P
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Efferth T
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.

MeSH

Antineoplastic Agents, PhytogenicApoptosisCell Line, TumorChalconesDrug Resistance, MultipleDrug Resistance, NeoplasmFlavonoidsHep G2 CellsHumansInhibitory Concentration 50Membrane Potential, MitochondrialMolecular StructurePlant ExtractsPolygonumReactive Oxygen Species

Pub Type(s)

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

Language

eng

PubMed ID

25442273

Citation

Kuete, Victor, et al. "Cytotoxicity and Modes of Action of 4'-hydroxy-2',6'-dimethoxychalcone and Other Flavonoids Toward Drug-sensitive and Multidrug-resistant Cancer Cell Lines." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 21, no. 12, 2014, pp. 1651-7.
Kuete V, Nkuete AH, Mbaveng AT, et al. Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines. Phytomedicine. 2014;21(12):1651-7.
Kuete, V., Nkuete, A. H., Mbaveng, A. T., Wiench, B., Wabo, H. K., Tane, P., & Efferth, T. (2014). Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 21(12), 1651-7. https://doi.org/10.1016/j.phymed.2014.08.001
Kuete V, et al. Cytotoxicity and Modes of Action of 4'-hydroxy-2',6'-dimethoxychalcone and Other Flavonoids Toward Drug-sensitive and Multidrug-resistant Cancer Cell Lines. Phytomedicine. 2014 Oct 15;21(12):1651-7. PubMed PMID: 25442273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines. AU - Kuete,Victor, AU - Nkuete,Antoine H L, AU - Mbaveng,Armelle T, AU - Wiench,Benjamin, AU - Wabo,Hippolyte K, AU - Tane,Pierre, AU - Efferth,Thomas, Y1 - 2014/09/15/ PY - 2014/06/06/received PY - 2014/07/17/revised PY - 2014/08/16/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/3/31/medline KW - Anticancer KW - Apoptosis KW - Chalcones KW - Flavanones KW - Mode of action KW - Resistance SP - 1651 EP - 7 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 21 IS - 12 N2 - INTRODUCTION: Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4'-hydroxy-2',6'-dimethoxychalcone (1), cardamomin (2), 2',4'-dihydroxy-3',6'-dimethoxychalcone (3)], and four flavanones [(S)-(-)-pinostrobin (4), (S)-(-)-onysilin (5) and alpinetin (6)] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types. METHODS: The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometry for the mechanistic studies of the most active molecule (1). RESULTS: IC50 values in a range of 2.54 μM against CEM/ADR5000 leukemia cells to 58.63 μM toward hepatocarcinoma HepG2 cells were obtained with 1. The lowest IC50 values of 8.59 μM for 2 and 10.67 μM for 3 were found against CCRF-CEM cells leukemia cells, whilst the corresponding values were above 80 μM for 4 and 6. P-glycoprotein-expressing and multidrug-resistant CEM/ADR5000 cells were much more sensitive toward compound 1 than toward doxorubicin and low cross-resistance or even collateral sensitivity was observed in other drug-resistent cell lines to this compound. Normal liver AML12 cells were more resistant to the studied compounds than HepG2 liver cancer cells, indicating tumor specificity at least to some extent. Compound 1 arrested the cell cycle between Go/G1 phase, strongly induced apoptosis via disrupted mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in the studied leukemia cell line. CONCLUSIONS: Chalcone 1 was the best tested cytotoxic molecule and further studies will be performed in order to envisage its possible use in the fight against multifactorial resistant cancer cells. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/25442273/Cytotoxicity_and_modes_of_action_of_4'_hydroxy_2'6'_dimethoxychalcone_and_other_flavonoids_toward_drug_sensitive_and_multidrug_resistant_cancer_cell_lines_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓18]

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