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

Kluska, Magdalena; Juszczak, M.; Żuchowski, Jerzy; Stochmal, Anna; Woźniak, Katarzyna

doi:10.3390/ijms22073520

Cited by 18 publications

(23 citation statements)

References 44 publications

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“…In our previous papers, we analyzed the impact of kaempferol and its glycoside derivatives isolated from Lens culinaris Medik. on HL-60 cells and PBMCs (peripheral blood mononuclear cells) treated with etoposide [28,29]. We demonstrated that kaempferol glycosides reduced the DNA damage induced by etoposide in PBMCs, but they did not have an impact on the DNA damage in HL-60 leukemic cells [28].…”

Section: Introductionmentioning

confidence: 81%

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

et al. 2022

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Kaempferol is a well-known antioxidant found in many plants and plant-based foods. In plants, kaempferol is present mainly in the form of glycoside derivatives. In this work, we focused on determining the effect of kaempferol and its glycoside derivatives on the expression level of genes related to the reduction of oxidative stress—NFE2L2, NQO1, SOD1, SOD2, and HO-1; the enzymatic activity of superoxide dismutases; and the level of glutathione. We used HL-60 acute promyelocytic leukemia cells, which were incubated with the anticancer drug etoposide and kaempferol or one of its three glycoside derivatives isolated from the aerial parts of Lens culinaris Medik.—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). We showed that none of the tested compounds affected NFE2L2 gene expression. Co-incubation with etoposide (1 µM) and kaempferol (10 and 50 µg/mL) leads to an increase in the expression of the HO-1 (9.49 and 9.33-fold at 10 µg/mL and 50 µg/mL, respectively), SOD1 (1.68-fold at 10 µg/mL), SOD2 (1.72-fold at 10–50 µg/mL), and NQO1 (1.84-fold at 50 µg/mL) genes in comparison to cells treated only with etoposide. The effect of kaempferol derivatives on gene expression differs depending on the derivative. All tested polyphenols increased the SOD activity in cells co-incubated with etoposide. We observed that the co-incubation of HL-60 cells with etoposide and kaempferol or derivative P7 increases the level of total glutathione in these cells. Taken together, our observations suggest that the antioxidant activity of kaempferol is related to the activation of antioxidant genes and proteins. Moreover, we observed that glycoside derivatives can have a different effect on the antioxidant cellular systems than kaempferol.

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Section: Introductionmentioning

confidence: 81%

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

et al. 2022

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“…Moreover, the investigated flavonols at a concentration range of 5–50 µM neither protected UN-SH-SY5Y and RA-SH-SY5Y cells against Dox-evoked damage nor potentiated the Dox cytotoxicity. Kaempferol and several of its glycosides, however, can potentiate the cytotoxic action of the antineoplastic agent etoposide as it was shown recently by Kluska and coworkers in HL-60 cells [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Jantas

Malarz

et al. 2021

IJMS

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As components of the human diet with potential health benefits, flavonols are the subject of numerous studies, confirming their antioxidant, free radical scavenging and anti-inflammatory activity. Taking into consideration the postulated pathogenesis of certain CNS dysfunctions characterized by neuronal degradation, flavonols may prevent the decay of neurons in multiple pathways. Leaves of Maesa membranacea yielded several flavonol glycosides including α-rhamnoisorobin (kaempferol 7-O-α-rhamnoside) and kaempferitrin (kaempferol 3,7-di-O-α-rhamnoside). The latter compound was a major constituent of the investigated plant material. Neuroprotective effects of kaempferitrin and α-rhamnoisorobin were tested in vitro using H2O2-, 6-OHDA- and doxorubicin-induced models of SH-SY5Y cell damage. Both undifferentiated and differentiated neuroblastoma cells were used in the experiments. α-Rhamnoisorobin at a concentration range of 1–10 µM demonstrated cytoprotective effects against H2O2-induced cell damage. The compound (at 1–10 µM) was also effective in attenuating 6-OHDA-induced neurotoxicity. In both H2O2- and 6-OHDA-induced cell damage, kaempferitrin, similar to isoquercitrin, demonstrated neuroprotective activity at the highest of the tested concentrations (50 µM). The tested flavonols were not effective in counteracting doxorubicin-induced cytotoxicity. Their caspase-3- and cathepsin D-inhibitory activities appeared to be structure dependent. Inhibition of the PI3-K/Akt pathway abolished the neuroprotective effect of the investigated flavonols.

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“…Three ATCC (Manassas, VA, USA) human leukemia cell lines were chosen, namely AML (acute promyelocytic HL-60 [ 27 ] and chronic myelogenous K-562 [ 28 ]), and ALL (T-cell acute lymphocytic MOLT-4 [ 23 ]) types. They were cultured with RPMI medium (Gibco; Grand Island, NY, USA) and mixed with 10% FBS and antibiotics (50 U/mL penicillin and 50 μg/mL streptomycin).…”

Section: Methodsmentioning

confidence: 99%

Nepenthes Ethyl Acetate Extract Provides Oxidative Stress-Dependent Anti-Leukemia Effects

et al. 2021

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Several kinds of solvents have been applied to Nepenthes extractions exhibiting antioxidant and anticancer effects. However, they were rarely investigated for Nepenthes ethyl acetate extract (EANT), especially leukemia cells. The purpose of the present study was to evaluate the antioxidant properties and explore the antiproliferation impact and mechanism of EANT in leukemia cells. Five standard assays demonstrated that EANT exhibits antioxidant capability. In the cell line model, EANT dose-responsively inhibited cell viabilities of three leukemia cell lines (HL-60, K-562, and MOLT-4) based on 24 h MTS assays, which were reverted by pretreating oxidative stress and apoptosis inhibitors (N-acetylcysteine and Z-VAD-FMK). Due to similar sensitivities among the three cell lines, leukemia HL-60 cells were chosen for exploring antiproliferation mechanisms. EANT caused subG1 and G1 cumulations, triggered annexin V-detected apoptosis, activated apoptotic caspase 3/7 activity, and induced poly ADP-ribose polymerase expression. Moreover, reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization were generated by EANT, which was reverted by N-acetylcysteine. The antioxidant response to oxidative stress showed that EANT upregulated mRNA expressions for nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), thioredoxin (TXN), heme oxygenase 1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1) genes. Moreover, these oxidative stresses led to DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) and were alleviated by N-acetylcysteine. Taken together, EANT demonstrated oxidative stress-dependent anti-leukemia ability to HL-60 cells associated with apoptosis and DNA damage.

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

Cited by 18 publications

References 44 publications

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Nepenthes Ethyl Acetate Extract Provides Oxidative Stress-Dependent Anti-Leukemia Effects

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