Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer

@article{Zhu2015AntiandrogensIA,
  title={Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer},
  author={Yezi Zhu and Chengfei Liu and Cameron M. Armstrong and Wei Lou and Amandeep Sandher and Allen C. Gao},
  journal={Clinical Cancer Research},
  year={2015},
  volume={21},
  pages={4133 - 4142}
}
Purpose: Previous studies show that inhibition of ABCB1 expression overcomes acquired docetaxel resistance in C4-2B-TaxR cells. In this study, we examined whether antiandrogens, such as bicalutamide and enzalutamide, could inhibit ABCB1 activity and overcome resistance to docetaxel. Experimental Design: ABCB1 efflux activity was determined using a rhodamine efflux assay. ABCB1 ATPase activity was determined by Pgp-Glo assay systems. The effects of the antiandrogens bicalutamide and enzalutamide… Expand
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References

SHOWING 1-10 OF 52 REFERENCES
Inhibition of ABCB1 Expression Overcomes Acquired Docetaxel Resistance in Prostate Cancer
TLDR
Results suggest that overexpression of ABCB1 mediates acquired docetaxel resistance and targetingABCB1 expression could be a potential approach to resensitize docetxel-resistant prostate cancer cells to docetAXel treatment. Expand
Sildenafil reverses ABCB1- and ABCG2-mediated chemotherapeutic drug resistance.
TLDR
It is reported that sildenafil has differential effects on cell surface ABC transporters such as ABCB1, ABCC1, and ABCG2 that modulate intracompartmental and intracellular concentrations of chemotherapeutic drugs. Expand
Niclosamide Inhibits Androgen Receptor Variants Expression and Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer
TLDR
These findings offer preclinical validation of niclosamide as a promising inhibitor of AR variants to treat, either alone or in combination with current antiandrogen therapies, patients with advanced prostate cancer, especially those resistant to enzalutamide. Expand
Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein.
TLDR
Twenty tRAs, selected based on modulation of paclitaxel cytotoxicity in Pgp-overexpressing MDA435/LCC6(mdr1) cells, were studied for modulation of retention and cytot toxicity of substrates of MRP-1 and BCRP as well as Pgp in established cell lines overexpressing each of these transporters. Expand
Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7).
TLDR
This work found that the clinically valuable multikinase inhibitor sorafenib, and a natural alkaloid, cepharanthine, inhibited ABCC10 docetaxel transport activity, and concomitant use of these agents might restore the intracellular accumulation and potency ofABCC10-exported cytotoxic drugs, such as paclitaxel. Expand
Characterisation and manipulation of docetaxel resistant prostate cancer cell lines
TLDR
This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxe-resistance which may represent an appropriate therapeutic target. Expand
HG-829 is a potent noncompetitive inhibitor of the ATP-binding cassette multidrug resistance transporter ABCB1.
TLDR
Findings indicate that HG-829 is a potent, long-acting, and noncompetitive modulator of P-glycoprotein export function that may offer therapeutic promise for multidrug-resistant malignancies. Expand
ABC multidrug transporters: structure, function and role in chemoresistance.
  • F. Sharom
  • Biology, Medicine
  • Pharmacogenomics
  • 2008
TLDR
Three ATP-binding cassette (ABC)-superfamily multidrug efflux pumps are known to be responsible for chemoresistance and the effect of various genotypes and haplotypes on the expression and function of these proteins is not yet clear, and their true impact remains controversial. Expand
Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer.
TLDR
It is shown that in addition to blocking cell division, docetaxel impairs AR signaling, evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer. Expand
Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.
TLDR
This work identified a subpopulation of cells that survive Docetaxel exposure that lacks differentiation markers and HLA class I (HLAI) antigens, while overexpressing the Notch and Hedgehog signaling pathways, and exhibited potent tumor-initiating capacity, establishing a link between chemotherapy resistance and tumor progression. Expand
...
1
2
3
4
5
...