P-glycoprotein mediates profound resistance to bisantrene

X. P. Zhang; M. K. Ritke; J. C. Yalowich; M. L. Slovak; J. Pelkey Ho; K. I. Collins; T. Annable; R. J. Arceci; F. E. Durr; L. M. Greenberger

P-glycoprotein mediates profound resistance to bisantrene

X. P. Zhang, M. K. Ritke, J. C. Yalowich, M. L. Slovak, J. Pelkey Ho, K. I. Collins, T. Annable, R. J. Arceci, F. E. Durr, L. M. Greenberger

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.

Original language	English (US)
Pages (from-to)	291-301
Number of pages	11
Journal	Oncology Research
Volume	6
Issue number	7
State	Published - 1994
Externally published	Yes

Keywords

P-glycoprotein
bisantrene
multidrug resistance
topoisomerase

ASJC Scopus subject areas

Medicine(all)

Cite this

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title = "P-glycoprotein mediates profound resistance to bisantrene",

abstract = "Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.",

keywords = "P-glycoprotein, bisantrene, multidrug resistance, topoisomerase",

author = "Zhang, {X. P.} and Ritke, {M. K.} and Yalowich, {J. C.} and Slovak, {M. L.} and Ho, {J. Pelkey} and Collins, {K. I.} and T. Annable and Arceci, {R. J.} and Durr, {F. E.} and Greenberger, {L. M.}",

year = "1994",

language = "English (US)",

volume = "6",

pages = "291--301",

journal = "Oncology Research",

issn = "0965-0407",

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TY - JOUR

T1 - P-glycoprotein mediates profound resistance to bisantrene

AU - Zhang, X. P.

AU - Ritke, M. K.

AU - Yalowich, J. C.

AU - Slovak, M. L.

AU - Ho, J. Pelkey

AU - Collins, K. I.

AU - Annable, T.

AU - Arceci, R. J.

AU - Durr, F. E.

AU - Greenberger, L. M.

PY - 1994

Y1 - 1994

N2 - Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.

AB - Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.

KW - P-glycoprotein

KW - bisantrene

KW - multidrug resistance

KW - topoisomerase

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AN - SCOPUS:0028130505

SN - 0965-0407

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JO - Oncology Research

JF - Oncology Research

IS - 7

ER -

P-glycoprotein mediates profound resistance to bisantrene

Abstract

Keywords

ASJC Scopus subject areas

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