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The ABCs and HSPs of Breast Cancer: Researchers Target MDR and Stress Proteins to Reverse Chemoresistance and Cardiotoxicity

Tags: Cancer, Toxicology,

ATP-binding cassette (ABC) transporters belong to a highly conserved superfamily of transmembrane proteins involved in the efflux of a variety of substrates, including chemotherapeutic drugs such as doxorubicin, out of the cell. Expression of the transporters P-glycoprotein (MDR1, ABCB1), MRP1 (ABCC1) and BCRP (ABCG2) is up-regulated in a majority of cancers, a phenomenon linked to the accumulation of mutant p53 and its atypical transcriptional activity in cooperation with NFkB. Although an effective antineoplastic, doxorubicin has unwanted side effects, particularly cardiotoxicity that can lead to congestive heart failure.

In two recent publications in The Journal of Biological Chemistry, and The Proceedings of the National Academy of Sciences, Dr. Govindasamy Ilangovan of The Ohio State University and colleagues shed light on the role of the small heat shock protein HSP27 and the stress-inducible transcription factor HSF-1 in these two unwanted outcomes. In the first, the authors demonstrate that forced expression of HSP27 in a doxorubicin-resistant MCF-7 breast cancer cell line significantly reduced mutant p53 and NFκB levels, and mediated repressed expression of P-glycoprotein. The net effect was decreased drug efflux and increased apoptosis, demonstrating the potential therapeutic benefit of modulating HSP27 expression in tumor cells to reduce chemoresistance.

In the second, the authors describe an interesting twist: increasing P-glycoprotein expression in cardiomyocytes via inhibition of HSF-1/NFκB transactivation appears to be part of a protective mechanism that could abrogate doxorubicin associated cardiotoxicity. Gene-based or pharmacological therapies targeting HSF-1 expression in the heart could enhance the effectiveness of such anti-cancer drugs by reducing their cardiotoxic side effects.

Enzo Life Sciences offers a comprehensive portfolio for studying the role of multidrug resistance and cell stress proteins in cancer, including live cell analysis kits, transporter-specific dyes, antibodies, and biochemicals (inhibitors and activators), some of which are briefly described below.

 

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EFLUXX-ID® Green multidrug resistance assay kit 

Simple No-wash Assay for  Simultaneous Monitoring of All 3 Major ABC Transporter Proteins – MDR, BCRP & MRP
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ENZ-51029-K100 1 Kit 538.00 USD
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HSF1 ELISA kit 

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HSP27 (human), ELISA kit 

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Only commercially available ELISA kit for ultra-sensitive detection of human phospho-Ser15 HSP27 in cell lysates, plasma, and serum.
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HSP70 ELISA kit 

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HSP70 high sensitivity ELISA kit 

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SCREEN-WELL® Cardiotoxicity library 

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SCREEN-WELL® Hematopoietic Toxicity library 

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Calcein AM (ultra pure) 

Calcium dye
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Hoechst 33342 (ultra pure) 

Cell permeable DNA dye
23491-52-3, ≥95% (HPLC) | Print as PDF
 
ENZ-52401 100 mg 128.00 USD
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Rhodamine 123 (ultra pure) 

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HSF1 monoclonal antibody (10H8) 

IHC (PS), WB | Print as PDF
 
ADI-SPA-950-D 50 µg 184.00 USD
 
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HSF1 polyclonal antibody 

ELISA, IP, WB, EMSA | Print as PDF
 
ADI-SPA-901-D 50 µg 161.00 USD
 
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[pSer326]HSF1 polyclonal antibody 

WB | Print as PDF
 
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HSP25 polyclonal antibody 

ICC, IF, IP, WB, Electron microscopy | Print as PDF
 
ADI-SPA-801-D 50 µg 161.00 USD
 
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HSP27 monoclonal antibody (G3.1) 

ELISA, ICC, IHC (PS), IP, WB, Electron microscopy, in vitro Assay | Print as PDF
 
ADI-SPA-800-D 50 µg 194.00 USD
 
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HSP27 polyclonal antibody 

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IF, IHC, WB | Print as PDF
 
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[pSer78]HSP27 polyclonal antibody 

IHC, WB | Print as PDF
 
ADI-SPA-523-D 50 µg 151.00 USD
 
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[pSer82]HSP27 polyclonal antibody 

IF, IP, WB | Print as PDF
 
ADI-SPA-524-D 50 µl 172.00 USD
 
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HSP70 (universal) monoclonal antibody (5A5) 

ICC, IF, IHC (FS), IP, WB, Gel Shift | Print as PDF
 
ALX-804-074-R250 250 µl 647.00 USD
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HSC70/HSP70 monoclonal antibody (BB70) 

IHC, IP, WB | Print as PDF
 
ADI-SPA-822-D 50 µg 194.00 USD
 
ADI-SPA-822-F 200 µg 389.00 USD
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HSC70/HSP70 polyclonal antibody 

IHC (PS), WB | Print as PDF
 
ADI-SPA-757-D 50 µg 140.00 USD
 
ADI-SPA-757-F 200 µg 345.00 USD
 
ADI-SPA-757-J 1 mg 1,300.00 USD
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ELISA, Flow Cytometry, ICC, IF, IHC, IP, WB, Electron microscopy | Print as PDF
 
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HSP70/HSP72 polyclonal antibody 

ICC, IF, IHC, IP, WB | Print as PDF
 
ADI-SPA-812-D 50 µg 161.00 USD
 
ADI-SPA-812-F 200 µg 356.00 USD
 
ADI-SPA-812-J 1 mg 1,456.00 USD
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HSP90 polyclonal antibody 

IHC (PS), WB | Print as PDF
 
ADI-SPA-836-D 50 µg 140.00 USD
 
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HSP90α monoclonal antibody (9D2) 

Flow Cytometry, ICC, IHC, IP, WB | Print as PDF
 
ADI-SPA-840-D 50 µg 172.00 USD
 
ADI-SPA-840-F 200 µg 389.00 USD
 
ADI-SPA-840-J 1 mg 1,566.00 USD
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HSP90α polyclonal antibody 

IHC, WB, Cell migration, Inhibition assay | Print as PDF
 
ADI-SPS-771-D 50 µg 151.00 USD
 
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HSP90β monoclonal antibody (K3705) 

IHC, WB | Print as PDF
 
ADI-SPA-842-D 50 µg 194.00 USD
 
ADI-SPA-842-F 200 µg 410.00 USD
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HSP90β polyclonal antibody 

WB | Print as PDF
 
ADI-SPA-844-050 50 µg 151.00 USD
 
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HSP90α/β monoclonal antibody (H90-10) 

ICC, IP, WB | Print as PDF
 
ALX-804-808-C100 100 µg 269.00 USD
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MDR3 P-glycoprotein (human) monoclonal antibody (P3II-26) 

ICC, IHC (FS), WB | Print as PDF
 
ALX-801-028-C125 125 µg 453.00 USD
 
ALX-801-028-C250 250 µg 777.00 USD
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P-glycoprotein (human) monoclonal antibody (C494) 

Flow Cytometry, ICC, IHC (FS), IHC (PS), IP, WB | Print as PDF
 
ALX-801-003-C100 1 ml 1,004.00 USD
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P-glycoprotein (human) monoclonal antibody (JSB-1) 

Flow Cytometry, ICC, IHC (FS), IHC (PS) | Print as PDF
 
ALX-801-004-C125 125 µg 453.00 USD
 
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P-glycoprotein (human) monoclonal antibody (MRK16) 

Flow Cytometry, IHC (FS), IP, FUNC | Print as PDF
 
ALX-801-008-C150 150 µg 1,057.00 USD
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ICC, IHC (FS), IHC (PS), IP | Print as PDF
 
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