Open Access

Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia

  • Authors:
    • Gulsum Akgun-Cagliyan
    • Aysegul Cort-Donmez
    • Emine Kilic-Toprak
    • Fatih Altintas
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  • Published online on: June 14, 2022     https://doi.org/10.3892/etm.2022.11441
  • Article Number: 514
  • Copyright: © Akgun-Cagliyan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Verbascoside (Verb) may exhibit potential antitumour activities in leukaemia. The present study investigated the effect of Verb, in combination with imatinib (IM), dasatinib (Das), lipopolysaccharide (LPS) and TNF, on cell survival, Abl expression, apoptosis, oxidative stress and the MAPK pathway in chronic myeloid leukaemia (CML) cells. Cell viability was determined using the WST‑8 assay in K562 and R‑K562 cells treated with Verb and/or IM, Das, LPS and TNF. Apoptosis and DNA damage in CML cells was detected by caspase‑3 and comet analysis. The protein levels of Abl (Phospho‑Tyr412), and total/phosphorylated p38, JNK and ERK in CML cells were analysed using a Colorimetric Cell‑Based Assay. Oxidative stress was examined using total antioxidant and oxidant status assays. Treatment with Verb and/or tyrosine kinase inhibitors (TKIs), LPS and TNF resulted in a significant decrease in the Tyr‑412 phosphorylation of Abl in K562 and R‑K562 cells. In addition, cotreatment with Verb and IM or Das additively induced apoptosis by activating caspase‑3 levels in both cell lines. Activation of p38 and JNK can result in growth arrest and cell death, whereas ERK stimulation results in cell division and differentiation. The present study demonstrated that cotreatment with Verb and TKIs suppressed phosphorylated‑ERK1/2, whereas the levels of phosphorylated‑p‑38 and phosphorylated‑JNK were significantly elevated by Verb and/or IM, Das, LPS and TNF, thus suggesting that Abl and Src inhibition could be involved in the effects of Verb on MAPK signalling in R‑K562 cells. Furthermore, Verb elevated reactive oxygen species levels additively with TKIs in both cell lines by increasing the oxidant capacity and decreasing the antioxidant capacity. In conclusion, anti‑leukemic mechanisms of Verb may be mediated by Abl protein and regulation of its downstream p38-MAPK/JNK pathway, caspase‑3 and oxidative stress in CML cells.
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August-2022
Volume 24 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Akgun-Cagliyan G, Cort-Donmez A, Kilic-Toprak E and Altintas F: Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia. Exp Ther Med 24: 514, 2022
APA
Akgun-Cagliyan, G., Cort-Donmez, A., Kilic-Toprak, E., & Altintas, F. (2022). Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia. Experimental and Therapeutic Medicine, 24, 514. https://doi.org/10.3892/etm.2022.11441
MLA
Akgun-Cagliyan, G., Cort-Donmez, A., Kilic-Toprak, E., Altintas, F."Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia". Experimental and Therapeutic Medicine 24.2 (2022): 514.
Chicago
Akgun-Cagliyan, G., Cort-Donmez, A., Kilic-Toprak, E., Altintas, F."Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia". Experimental and Therapeutic Medicine 24, no. 2 (2022): 514. https://doi.org/10.3892/etm.2022.11441