Home > Research > Publications & Outputs > Jadomycins are cytotoxic to ABCB1-, ABCC1-, and...

Research

Links

Text available via DOI:

Keywords

View graph of relations

Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. / Issa, Mark E; Hall, Steven R; Dupuis, Stephanie N et al.
In: Anti-Cancer Drugs, Vol. 25, No. 3, 01.03.2014, p. 255-69.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Issa, ME, Hall, SR, Dupuis, SN, Graham, CL, Jakeman, DL & Goralski, KB 2014, 'Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells', Anti-Cancer Drugs, vol. 25, no. 3, pp. 255-69. https://doi.org/10.1097/CAD.0000000000000043

APA

Issa, M. E., Hall, S. R., Dupuis, S. N., Graham, C. L., Jakeman, D. L., & Goralski, K. B. (2014). Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. Anti-Cancer Drugs, 25(3), 255-69. https://doi.org/10.1097/CAD.0000000000000043

Vancouver

Issa ME, Hall SR, Dupuis SN, Graham CL, Jakeman DL, Goralski KB. Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. Anti-Cancer Drugs. 2014 Mar 1;25(3):255-69. doi: 10.1097/CAD.0000000000000043

Author

Issa, Mark E ; Hall, Steven R ; Dupuis, Stephanie N et al. / Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. In: Anti-Cancer Drugs. 2014 ; Vol. 25, No. 3. pp. 255-69.

Bibtex

@article{6c71673dce72497e8e1a0e906e47e171,
title = "Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells",
abstract = "Multidrug resistance remains a major obstacle in the effective treatment of metastatic breast cancer. One mechanism by which multidrug resistance is conferred is the decreased intracellular drug accumulation due to the upregulation of the ATP-binding cassette (ABC) transporters. We have previously demonstrated that jadomycins, polyketide-derived natural products produced by Streptomyces venezuelae ISP5230, inhibit the growth of the human breast ductal carcinoma cell lines T47D and MDA-MB-435. To expand our understanding of jadomycin pharmacology, the goal of the present study was to determine whether the function of ABC efflux transporters affects the anticancer activity of jadomycins to MCF7 breast cancer cells. Seven jadomycin analogs (DNV, B, L, SPhG, F, S, and T) effectively reduced the viability of MCF7 control and ABCB1-, ABCC1-, or ABCG2-overexpressing drug-resistant MCF7 breast cancer cells as measured by methyltetrazolium cell viability assays and lactate dehydrogenase cytotoxicity assays. The inhibition of ABCB1, ABCC1, or ABCG2 with verapamil, MK-571, or Ko-143, respectively, did not augment the cytotoxicity of jadomycins DNV, B, L, SPhG, F, S, or T in drug-resistant MCF7 cells. Furthermore, jadomycins B, L, SPhG, F, S, and T did not increase the intracellular accumulation of ABCB1, ABCC1, or ABCG2 fluorescent substrates in HEK-293 cells stably transfected with ABCB1, ABCC1, or ABCG2. We conclude that jadomycins B, L, SPhG, F, S, and T are effective agents in the eradication of MCF7 breast cancer cells grown in culture, and that their cytotoxicities are minimally affected by ABCB1, ABCC1, and ABCG2 efflux transporter function.",
keywords = "ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters/metabolism, Antibiotics, Antineoplastic/pharmacology, Aurora Kinase B/antagonists & inhibitors, Breast Neoplasms, Cell Survival/drug effects, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Female, Humans, MCF-7 Cells, Multidrug Resistance-Associated Proteins/metabolism, Neoplasm Proteins/metabolism, Polyketides/chemistry",
author = "Issa, {Mark E} and Hall, {Steven R} and Dupuis, {Stephanie N} and Graham, {Cathy L} and Jakeman, {David L} and Goralski, {Kerry B}",
year = "2014",
month = mar,
day = "1",
doi = "10.1097/CAD.0000000000000043",
language = "English",
volume = "25",
pages = "255--69",
journal = "Anti-Cancer Drugs",
issn = "0959-4973",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

RIS

TY - JOUR

T1 - Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells

AU - Issa, Mark E

AU - Hall, Steven R

AU - Dupuis, Stephanie N

AU - Graham, Cathy L

AU - Jakeman, David L

AU - Goralski, Kerry B

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Multidrug resistance remains a major obstacle in the effective treatment of metastatic breast cancer. One mechanism by which multidrug resistance is conferred is the decreased intracellular drug accumulation due to the upregulation of the ATP-binding cassette (ABC) transporters. We have previously demonstrated that jadomycins, polyketide-derived natural products produced by Streptomyces venezuelae ISP5230, inhibit the growth of the human breast ductal carcinoma cell lines T47D and MDA-MB-435. To expand our understanding of jadomycin pharmacology, the goal of the present study was to determine whether the function of ABC efflux transporters affects the anticancer activity of jadomycins to MCF7 breast cancer cells. Seven jadomycin analogs (DNV, B, L, SPhG, F, S, and T) effectively reduced the viability of MCF7 control and ABCB1-, ABCC1-, or ABCG2-overexpressing drug-resistant MCF7 breast cancer cells as measured by methyltetrazolium cell viability assays and lactate dehydrogenase cytotoxicity assays. The inhibition of ABCB1, ABCC1, or ABCG2 with verapamil, MK-571, or Ko-143, respectively, did not augment the cytotoxicity of jadomycins DNV, B, L, SPhG, F, S, or T in drug-resistant MCF7 cells. Furthermore, jadomycins B, L, SPhG, F, S, and T did not increase the intracellular accumulation of ABCB1, ABCC1, or ABCG2 fluorescent substrates in HEK-293 cells stably transfected with ABCB1, ABCC1, or ABCG2. We conclude that jadomycins B, L, SPhG, F, S, and T are effective agents in the eradication of MCF7 breast cancer cells grown in culture, and that their cytotoxicities are minimally affected by ABCB1, ABCC1, and ABCG2 efflux transporter function.

AB - Multidrug resistance remains a major obstacle in the effective treatment of metastatic breast cancer. One mechanism by which multidrug resistance is conferred is the decreased intracellular drug accumulation due to the upregulation of the ATP-binding cassette (ABC) transporters. We have previously demonstrated that jadomycins, polyketide-derived natural products produced by Streptomyces venezuelae ISP5230, inhibit the growth of the human breast ductal carcinoma cell lines T47D and MDA-MB-435. To expand our understanding of jadomycin pharmacology, the goal of the present study was to determine whether the function of ABC efflux transporters affects the anticancer activity of jadomycins to MCF7 breast cancer cells. Seven jadomycin analogs (DNV, B, L, SPhG, F, S, and T) effectively reduced the viability of MCF7 control and ABCB1-, ABCC1-, or ABCG2-overexpressing drug-resistant MCF7 breast cancer cells as measured by methyltetrazolium cell viability assays and lactate dehydrogenase cytotoxicity assays. The inhibition of ABCB1, ABCC1, or ABCG2 with verapamil, MK-571, or Ko-143, respectively, did not augment the cytotoxicity of jadomycins DNV, B, L, SPhG, F, S, or T in drug-resistant MCF7 cells. Furthermore, jadomycins B, L, SPhG, F, S, and T did not increase the intracellular accumulation of ABCB1, ABCC1, or ABCG2 fluorescent substrates in HEK-293 cells stably transfected with ABCB1, ABCC1, or ABCG2. We conclude that jadomycins B, L, SPhG, F, S, and T are effective agents in the eradication of MCF7 breast cancer cells grown in culture, and that their cytotoxicities are minimally affected by ABCB1, ABCC1, and ABCG2 efflux transporter function.

KW - ATP Binding Cassette Transporter, Subfamily B

KW - ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism

KW - ATP Binding Cassette Transporter, Subfamily G, Member 2

KW - ATP-Binding Cassette Transporters/metabolism

KW - Antibiotics, Antineoplastic/pharmacology

KW - Aurora Kinase B/antagonists & inhibitors

KW - Breast Neoplasms

KW - Cell Survival/drug effects

KW - Drug Resistance, Multiple

KW - Drug Resistance, Neoplasm

KW - Drug Screening Assays, Antitumor

KW - Female

KW - Humans

KW - MCF-7 Cells

KW - Multidrug Resistance-Associated Proteins/metabolism

KW - Neoplasm Proteins/metabolism

KW - Polyketides/chemistry

U2 - 10.1097/CAD.0000000000000043

DO - 10.1097/CAD.0000000000000043

M3 - Journal article

C2 - 24231527

VL - 25

SP - 255

EP - 269

JO - Anti-Cancer Drugs

JF - Anti-Cancer Drugs

SN - 0959-4973

IS - 3

ER -