A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance

Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Megumi Tsukamoto [verfasserIn] Miho Yamashita [verfasserIn] Tsuyoshi Nishi [verfasserIn] Hiroshi Nakagawa [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP

Übergeordnetes Werk:	In: Cells - MDPI AG, 2012, 8(2019), 1, p 39
Übergeordnetes Werk:	volume:8 ; year:2019 ; number:1, p 39

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cells8010039

Katalog-ID:	DOAJ060424702

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allfields	10.3390/cells8010039 doi (DE-627)DOAJ060424702 (DE-599)DOAJc3774ef575a546e1a7403d5f29dd30fb DE-627 ger DE-627 rakwb eng QH301-705.5 Megumi Tsukamoto verfasserin aut A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance. ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP Biology (General) Miho Yamashita verfasserin aut Tsuyoshi Nishi verfasserin aut Hiroshi Nakagawa verfasserin aut In Cells MDPI AG, 2012 8(2019), 1, p 39 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:8 year:2019 number:1, p 39 https://doi.org/10.3390/cells8010039 kostenfrei https://doaj.org/article/c3774ef575a546e1a7403d5f29dd30fb kostenfrei http://www.mdpi.com/2073-4409/8/1/39 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1, p 39
spelling	10.3390/cells8010039 doi (DE-627)DOAJ060424702 (DE-599)DOAJc3774ef575a546e1a7403d5f29dd30fb DE-627 ger DE-627 rakwb eng QH301-705.5 Megumi Tsukamoto verfasserin aut A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance. ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP Biology (General) Miho Yamashita verfasserin aut Tsuyoshi Nishi verfasserin aut Hiroshi Nakagawa verfasserin aut In Cells MDPI AG, 2012 8(2019), 1, p 39 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:8 year:2019 number:1, p 39 https://doi.org/10.3390/cells8010039 kostenfrei https://doaj.org/article/c3774ef575a546e1a7403d5f29dd30fb kostenfrei http://www.mdpi.com/2073-4409/8/1/39 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1, p 39
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allfieldsGer	10.3390/cells8010039 doi (DE-627)DOAJ060424702 (DE-599)DOAJc3774ef575a546e1a7403d5f29dd30fb DE-627 ger DE-627 rakwb eng QH301-705.5 Megumi Tsukamoto verfasserin aut A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance. ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP Biology (General) Miho Yamashita verfasserin aut Tsuyoshi Nishi verfasserin aut Hiroshi Nakagawa verfasserin aut In Cells MDPI AG, 2012 8(2019), 1, p 39 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:8 year:2019 number:1, p 39 https://doi.org/10.3390/cells8010039 kostenfrei https://doaj.org/article/c3774ef575a546e1a7403d5f29dd30fb kostenfrei http://www.mdpi.com/2073-4409/8/1/39 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1, p 39
allfieldsSound	10.3390/cells8010039 doi (DE-627)DOAJ060424702 (DE-599)DOAJc3774ef575a546e1a7403d5f29dd30fb DE-627 ger DE-627 rakwb eng QH301-705.5 Megumi Tsukamoto verfasserin aut A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance. ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP Biology (General) Miho Yamashita verfasserin aut Tsuyoshi Nishi verfasserin aut Hiroshi Nakagawa verfasserin aut In Cells MDPI AG, 2012 8(2019), 1, p 39 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:8 year:2019 number:1, p 39 https://doi.org/10.3390/cells8010039 kostenfrei https://doaj.org/article/c3774ef575a546e1a7403d5f29dd30fb kostenfrei http://www.mdpi.com/2073-4409/8/1/39 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1, p 39
language	English
source	In Cells 8(2019), 1, p 39 volume:8 year:2019 number:1, p 39
sourceStr	In Cells 8(2019), 1, p 39 volume:8 year:2019 number:1, p 39
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institution	findex.gbv.de
topic_facet	ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP Biology (General)
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container_title	Cells
authorswithroles_txt_mv	Megumi Tsukamoto @@aut@@ Miho Yamashita @@aut@@ Tsuyoshi Nishi @@aut@@ Hiroshi Nakagawa @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Megumi Tsukamoto
spellingShingle	Megumi Tsukamoto misc QH301-705.5 misc ATP-binding cassette (ABC) transporter misc ABCC4 misc MRP4 misc SNP misc Biology (General) A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance
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topic_title	QH301-705.5 A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance ATP-binding cassette (ABC) transporter ABCC4 MRP4 SNP
topic	misc QH301-705.5 misc ATP-binding cassette (ABC) transporter misc ABCC4 misc MRP4 misc SNP misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc ATP-binding cassette (ABC) transporter misc ABCC4 misc MRP4 misc SNP misc Biology (General)
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title	A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance
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title_full	A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance
author_sort	Megumi Tsukamoto
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author_browse	Megumi Tsukamoto Miho Yamashita Tsuyoshi Nishi Hiroshi Nakagawa
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title_sort	human abc transporter abcc4 gene snp (rs11568658, 559 g > t, g187w) reduces abcc4-dependent drug resistance
callnumber	QH301-705.5
title_auth	A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance
abstract	Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance.
abstractGer	Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance.
abstract_unstemmed	Broad-spectrum drug resistance is a major obstacle in cancer treatment, which is often caused by overexpression of ABC transporters the levels of which vary between individuals due to single-nucleotide polymorphisms (SNPs) in their genes. In the present study, we focused on the human ABC transporter ABCC4 and one major non-synonymous SNP variant of the ABCC4 gene in the Japanese population (rs11568658, 559 G > T, G187W) whose allele frequency is 12.5%. Cells expressing ABCC4 (G187W) were established using the Flp-In™ system based on Flp recombinase-mediated transfection to quantitatively evaluate the impacts of this non-synonymous SNP on drug resistance profiles of the cells. Cells expressing ABCC4 (WT) or (G187W) showed comparable ABCC4 mRNA levels. 3-(4,5-Dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that the EC50 value of the anticancer drug, SN-38, against cells expressing ABCC4 (G187W) was 1.84-fold lower than that against cells expressing ABCC4 (WT). Both azathioprine and 6-mercaptopurine showed comparable EC50 values against cells expressing ABCC4 (G187W) and those expressing ABCC4 (WT). These results indicate that the substitution of Gly at position 187 of ABCC4 to Trp resulted in reduced SN-38 resistance.
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title_short	A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance
url	https://doi.org/10.3390/cells8010039 https://doaj.org/article/c3774ef575a546e1a7403d5f29dd30fb http://www.mdpi.com/2073-4409/8/1/39 https://doaj.org/toc/2073-4409
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author2	Miho Yamashita Tsuyoshi Nishi Hiroshi Nakagawa
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up_date	2024-07-03T14:52:43.607Z
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A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G &gt; T, G187W) Reduces ABCC4-Dependent Drug Resistance

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A Human ABC Transporter ABCC4 Gene SNP (rs11568658, 559 G > T, G187W) Reduces ABCC4-Dependent Drug Resistance