Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells

Kaempferol is a polyphenol found in a variety of plants. Kaempferol exerts antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives—kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-...

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Main Authors: Magdalena Kluska, Michał Juszczak, Jerzy Żuchowski, Anna Stochmal, Katarzyna Woźniak
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/7/3520
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author Magdalena Kluska
Michał Juszczak
Jerzy Żuchowski
Anna Stochmal
Katarzyna Woźniak
author_facet Magdalena Kluska
Michał Juszczak
Jerzy Żuchowski
Anna Stochmal
Katarzyna Woźniak
author_sort Magdalena Kluska
collection DOAJ
description Kaempferol is a polyphenol found in a variety of plants. Kaempferol exerts antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives—kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7), isolated from aerial parts of <i>Lens culinaris</i> Medik.—affect the antitumor activity of etoposide in human promyelocytic leukemia (HL-60) cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol and its glycoside derivatives can modulate the activity of etoposide in HL-60 cells and affect its antitumor efficacy in this way. Kaempferol derivatives may have the opposite effect on the action of etoposide in HL-60 cells compared to kaempferol.
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spelling doaj.art-4eac2ac320f240e08413271916d1c7cb2023-11-21T13:14:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227352010.3390/ijms22073520Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 CellsMagdalena Kluska0Michał Juszczak1Jerzy Żuchowski2Anna Stochmal3Katarzyna Woźniak4Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandDepartment of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandDepartment of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation, State Research Institute, 24-100 Pulawy, PolandDepartment of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation, State Research Institute, 24-100 Pulawy, PolandDepartment of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandKaempferol is a polyphenol found in a variety of plants. Kaempferol exerts antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives—kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7), isolated from aerial parts of <i>Lens culinaris</i> Medik.—affect the antitumor activity of etoposide in human promyelocytic leukemia (HL-60) cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol and its glycoside derivatives can modulate the activity of etoposide in HL-60 cells and affect its antitumor efficacy in this way. Kaempferol derivatives may have the opposite effect on the action of etoposide in HL-60 cells compared to kaempferol.https://www.mdpi.com/1422-0067/22/7/3520kaempferoletoposideDNA damageapoptosiscell cycleoxidative stress
spellingShingle Magdalena Kluska
Michał Juszczak
Jerzy Żuchowski
Anna Stochmal
Katarzyna Woźniak
Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
International Journal of Molecular Sciences
kaempferol
etoposide
DNA damage
apoptosis
cell cycle
oxidative stress
title Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
title_full Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
title_fullStr Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
title_full_unstemmed Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
title_short Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
title_sort kaempferol and its glycoside derivatives as modulators of etoposide activity in hl 60 cells
topic kaempferol
etoposide
DNA damage
apoptosis
cell cycle
oxidative stress
url https://www.mdpi.com/1422-0067/22/7/3520
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AT jerzyzuchowski kaempferolanditsglycosidederivativesasmodulatorsofetoposideactivityinhl60cells
AT annastochmal kaempferolanditsglycosidederivativesasmodulatorsofetoposideactivityinhl60cells
AT katarzynawozniak kaempferolanditsglycosidederivativesasmodulatorsofetoposideactivityinhl60cells