Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo

Ryuta Yamazaki, Yukiko Nishiyama, Tomio Furuta, Hiroshi Hatano, Yoshiaki Igarashi, Naoyuki Asakawa, Hiroshi Kodaira, Hiroyuki Takahashi, Ritsuo Aiyama, Takeshi Matsuzaki, Nao Yagi, Yoshikazu Sugimoto

研究成果: Article

33 引用 (Scopus)

抄録

Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38 - resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1 - mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

元の言語English
ページ(範囲)1252-1263
ページ数12
ジャーナルMolecular Cancer Therapeutics
10
発行部数7
DOI
出版物ステータスPublished - 2011 7

Fingerprint

irinotecan
Acrylonitrile
Drug Resistance
Topotecan
Mitoxantrone
Prodrugs
P-Glycoprotein
Lung Neoplasms
Neoplasms
Leukemia P388
HCT116 Cells
K562 Cells
YHO-13177
In Vitro Techniques
YHO-13351
Paclitaxel
Pancreatic Neoplasms
Heterografts

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

これを引用

Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo. / Yamazaki, Ryuta; Nishiyama, Yukiko; Furuta, Tomio; Hatano, Hiroshi; Igarashi, Yoshiaki; Asakawa, Naoyuki; Kodaira, Hiroshi; Takahashi, Hiroyuki; Aiyama, Ritsuo; Matsuzaki, Takeshi; Yagi, Nao; Sugimoto, Yoshikazu.

:: Molecular Cancer Therapeutics, 巻 10, 番号 7, 07.2011, p. 1252-1263.

研究成果: Article

Yamazaki, R, Nishiyama, Y, Furuta, T, Hatano, H, Igarashi, Y, Asakawa, N, Kodaira, H, Takahashi, H, Aiyama, R, Matsuzaki, T, Yagi, N & Sugimoto, Y 2011, 'Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo', Molecular Cancer Therapeutics, 巻. 10, 番号 7, pp. 1252-1263. https://doi.org/10.1158/1535-7163.MCT-10-0874
Yamazaki, Ryuta ; Nishiyama, Yukiko ; Furuta, Tomio ; Hatano, Hiroshi ; Igarashi, Yoshiaki ; Asakawa, Naoyuki ; Kodaira, Hiroshi ; Takahashi, Hiroyuki ; Aiyama, Ritsuo ; Matsuzaki, Takeshi ; Yagi, Nao ; Sugimoto, Yoshikazu. / Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo. :: Molecular Cancer Therapeutics. 2011 ; 巻 10, 番号 7. pp. 1252-1263.
@article{ba439ea378a94ba68ba90ee0fa4951f3,
title = "Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo",
abstract = "Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38 - resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1 - mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.",
author = "Ryuta Yamazaki and Yukiko Nishiyama and Tomio Furuta and Hiroshi Hatano and Yoshiaki Igarashi and Naoyuki Asakawa and Hiroshi Kodaira and Hiroyuki Takahashi and Ritsuo Aiyama and Takeshi Matsuzaki and Nao Yagi and Yoshikazu Sugimoto",
year = "2011",
month = "7",
doi = "10.1158/1535-7163.MCT-10-0874",
language = "English",
volume = "10",
pages = "1252--1263",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo

AU - Yamazaki, Ryuta

AU - Nishiyama, Yukiko

AU - Furuta, Tomio

AU - Hatano, Hiroshi

AU - Igarashi, Yoshiaki

AU - Asakawa, Naoyuki

AU - Kodaira, Hiroshi

AU - Takahashi, Hiroyuki

AU - Aiyama, Ritsuo

AU - Matsuzaki, Takeshi

AU - Yagi, Nao

AU - Sugimoto, Yoshikazu

PY - 2011/7

Y1 - 2011/7

N2 - Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38 - resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1 - mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

AB - Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38 - resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1 - mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=79960144930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960144930&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-10-0874

DO - 10.1158/1535-7163.MCT-10-0874

M3 - Article

C2 - 21566063

AN - SCOPUS:79960144930

VL - 10

SP - 1252

EP - 1263

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 7

ER -