Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells

Abstract Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels...

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Autores principales:	Seyed Abbas Mirzaei, Somayeh Reiisi, Parmida Ghiasi Tabari, Abolfazl Shekari, Fatemeh Aliakbari, Elaheh Azadfallah, Fatemeh Elahian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/534d720ee60745529e4a16bb37e6cfbc
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spelling	oai:doaj.org-article:534d720ee60745529e4a16bb37e6cfbc2021-12-02T11:40:34ZBroad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells10.1038/s41598-018-21710-52045-2322https://doaj.org/article/534d720ee60745529e4a16bb37e6cfbc2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21710-5https://doaj.org/toc/2045-2322Abstract Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels were relatively measured. Finally, accumulation and efflux kinetics were conducted. The results revealed cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS analyses using fluorescent-labeled antibodies showed no significant change in the MDR-protein levels. Functional kinetics revealed significant block of MDR1, BCRP and MRP transporter in the presence of shikonin derivatives. Maximum accumulation fold changes was quantified to be 4.4 and consequently, acetoxyisovalerylshikonin pretreated EPG85.257RDB cells was chemosensitized to daunorubicin tension 3.1-fold. Although, the MDR blockage was reported to follow time- and cell-dependent patterns, MDR1, BCRP and MRP2 responses to the shikonins are concentration-independent. These data suggest uncompetitive transporter blockage behavior of these agents. The results indicated that shikonin derivatives stimulate uptake and reduce efflux of chemotherapeutic agents in the malignant cancer cells, suggesting that chemotherapy in combination with shikonin compounds may be beneficial to cancer cells that overexpress multidrug resistance transporters.Seyed Abbas MirzaeiSomayeh ReiisiParmida Ghiasi TabariAbolfazl ShekariFatemeh AliakbariElaheh AzadfallahFatemeh ElahianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seyed Abbas Mirzaei Somayeh Reiisi Parmida Ghiasi Tabari Abolfazl Shekari Fatemeh Aliakbari Elaheh Azadfallah Fatemeh Elahian Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
description	Abstract Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels were relatively measured. Finally, accumulation and efflux kinetics were conducted. The results revealed cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS analyses using fluorescent-labeled antibodies showed no significant change in the MDR-protein levels. Functional kinetics revealed significant block of MDR1, BCRP and MRP transporter in the presence of shikonin derivatives. Maximum accumulation fold changes was quantified to be 4.4 and consequently, acetoxyisovalerylshikonin pretreated EPG85.257RDB cells was chemosensitized to daunorubicin tension 3.1-fold. Although, the MDR blockage was reported to follow time- and cell-dependent patterns, MDR1, BCRP and MRP2 responses to the shikonins are concentration-independent. These data suggest uncompetitive transporter blockage behavior of these agents. The results indicated that shikonin derivatives stimulate uptake and reduce efflux of chemotherapeutic agents in the malignant cancer cells, suggesting that chemotherapy in combination with shikonin compounds may be beneficial to cancer cells that overexpress multidrug resistance transporters.
format	article
author	Seyed Abbas Mirzaei Somayeh Reiisi Parmida Ghiasi Tabari Abolfazl Shekari Fatemeh Aliakbari Elaheh Azadfallah Fatemeh Elahian
author_facet	Seyed Abbas Mirzaei Somayeh Reiisi Parmida Ghiasi Tabari Abolfazl Shekari Fatemeh Aliakbari Elaheh Azadfallah Fatemeh Elahian
author_sort	Seyed Abbas Mirzaei
title	Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
title_short	Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
title_full	Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
title_fullStr	Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
title_full_unstemmed	Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
title_sort	broad blocking of mdr efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/534d720ee60745529e4a16bb37e6cfbc
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Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells

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