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Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein

The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium-binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may...

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Autores principales: Yang, Liu, Li, Duo, Tang, Peiyan, Zuo, Yunfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924120/
https://www.ncbi.nlm.nih.gov/pubmed/31897118
http://dx.doi.org/10.3892/ol.2019.11083
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author Yang, Liu
Li, Duo
Tang, Peiyan
Zuo, Yunfei
author_facet Yang, Liu
Li, Duo
Tang, Peiyan
Zuo, Yunfei
author_sort Yang, Liu
collection PubMed
description The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium-binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may provide drugs with the potential to be used as multidrug resistance reversal agents with low toxicity and multi-target characteristics. The present study selected K562/DOX cells, a CML drug-resistant cell line, as a research model, and aimed to examine whether curcumin was able to reverse the resistance to doxorubicin (DOX), and elucidate the underlying molecular mechanisms. An MTT cytotoxicity assay indicated that curcumin at 0.5–2 µM reversed DOX resistance with a reversal index of 1.3–9.3. Western blot analysis revealed that curcumin treatment caused a downregulation of the expression of P-glycoprotein (P-gp) and S100A8 in a dose- and time-dependent manner. To study the internal association between S100A8 and P-gp, and the S100A8 role in drug resistance reversal, an RNA knockdown assay was conducted; however, S100A8 did not regulate the expression of P-gp or vice versa. After inhibiting the expression of S100A8 with specific small interfering RNA (si-S100A8), the sensitivity of K562/DOX cells to DOX was enhanced. In addition, si-S100A8 did not increase the intracellular accumulation of DOX, but increased the intracellular free calcium ion content, and the expression and activity of apoptosis-associated proteins, thereby inducing apoptosis. In conclusion, the present study suggested that inhibition of S100A8 expression increased DOX-induced apoptosis, and curcumin acted independently on S100A8 and P-gp to exert its drug resistance reversal effects
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spelling pubmed-69241202020-01-02 Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein Yang, Liu Li, Duo Tang, Peiyan Zuo, Yunfei Oncol Lett Articles The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium-binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may provide drugs with the potential to be used as multidrug resistance reversal agents with low toxicity and multi-target characteristics. The present study selected K562/DOX cells, a CML drug-resistant cell line, as a research model, and aimed to examine whether curcumin was able to reverse the resistance to doxorubicin (DOX), and elucidate the underlying molecular mechanisms. An MTT cytotoxicity assay indicated that curcumin at 0.5–2 µM reversed DOX resistance with a reversal index of 1.3–9.3. Western blot analysis revealed that curcumin treatment caused a downregulation of the expression of P-glycoprotein (P-gp) and S100A8 in a dose- and time-dependent manner. To study the internal association between S100A8 and P-gp, and the S100A8 role in drug resistance reversal, an RNA knockdown assay was conducted; however, S100A8 did not regulate the expression of P-gp or vice versa. After inhibiting the expression of S100A8 with specific small interfering RNA (si-S100A8), the sensitivity of K562/DOX cells to DOX was enhanced. In addition, si-S100A8 did not increase the intracellular accumulation of DOX, but increased the intracellular free calcium ion content, and the expression and activity of apoptosis-associated proteins, thereby inducing apoptosis. In conclusion, the present study suggested that inhibition of S100A8 expression increased DOX-induced apoptosis, and curcumin acted independently on S100A8 and P-gp to exert its drug resistance reversal effects D.A. Spandidos 2020-01 2019-11-13 /pmc/articles/PMC6924120/ /pubmed/31897118 http://dx.doi.org/10.3892/ol.2019.11083 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yang, Liu
Li, Duo
Tang, Peiyan
Zuo, Yunfei
Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title_full Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title_fullStr Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title_full_unstemmed Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title_short Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium-binding protein A8 and P-glycoprotein
title_sort curcumin increases the sensitivity of k562/dox cells to doxorubicin by targeting s100 calcium-binding protein a8 and p-glycoprotein
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924120/
https://www.ncbi.nlm.nih.gov/pubmed/31897118
http://dx.doi.org/10.3892/ol.2019.11083
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