EMAIL THIS PAGE TO A FRIEND

Oncotarget

Catalytic inhibitors of DNA topoisomerase II suppress the androgen receptor signaling and prostate cancer progression.


PMID 26009876

Abstract

Although the new generation of androgen receptor (AR) antagonists like enzalutamide (ENZ) prolong survival of metastatic castration-resistant prostate cancer (CRPC), AR-driven tumors eventually recur indicating that additional therapies are required to fully block AR function. Since DNA topoisomerase II (Topo II) was demonstrated to be essential for AR to initiate gene transcription, this study tested whether catalytic inhibitors of Topo II can block AR signaling and suppress ENZ-resistant CRPC growth. Using multiple prostate cancer cell lines, we showed that catalytic Topo II inhibitors, ICRF187 and ICRF193 inhibited transcription activities of the wild-type AR, mutant ARs (F876L and W741C) and the AR-V7 splice variant. ICRF187 and ICRF193 decreased AR recruitment to target promoters and reduced AR nuclear localization. Both ICRF187 and ICRF193 also inhibited cell proliferation and delayed cell cycling at the G2/M phase. ICRF187 inhibited tumor growth of castration-resistant LNCaP and 22RV1 xenografts as well as ENZ-resistant MR49F xenografts. We conclude that catalytic Topo II inhibitors can block AR signaling and inhibit tumor growth of CRPC xenografts, identifying a potential co-targeting approach using these inhibitors in combination with AR pathway inhibitors in CRPC.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1409018
Anti-AKR1B1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
AV48180
Anti-AKR1B1 antibody produced in rabbit, IgG fraction of antiserum
SAB2100091
Anti-AKR1B1 antibody produced in rabbit, affinity isolated antibody
HPA026425
Anti-AKR1B1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1410404
Anti-AKR1B1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1410405
Anti-AKR1B1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4500944
Anti-AKR1B1, C-Terminal antibody produced in rabbit, affinity isolated antibody
GW22855 Anti-Amphiregulin antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB4300382
Anti-AR (Ab-650) antibody produced in rabbit, affinity isolated antibody
SAB2100139
Anti-AR antibody produced in rabbit, affinity isolated antibody
SAB1405478
Anti-AREG antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA008720
Anti-AREG antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1410727
Anti-AREG antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1400100
Anti-FDXR antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
SAB1400101
Anti-FDXR antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
SAB2100807
Anti-FDXR antibody produced in rabbit, affinity isolated antibody
G6649
Genistein, synthetic, ≥98% (HPLC), powder
C15H10O5
G6776
Genistein, from Glycine max (soybean), ~98% (HPLC)
C15H10O5
SAB1402112
Monoclonal Anti-AKR1B1 antibody produced in mouse, clone 2D12, purified immunoglobulin, buffered aqueous solution
WH0000367M1
Monoclonal Anti-AR antibody produced in mouse, clone 1G3, purified immunoglobulin, buffered aqueous solution
SAB5300341 Monoclonal Anti-AR antibody produced in mouse, clone 1A9D12, ascites fluid
SAB5300342
Monoclonal Anti-AR antibody produced in mouse, clone 2H8, ascites fluid
SAB1402118
Monoclonal Anti-AREG antibody produced in mouse, clone 3E4, purified immunoglobulin, buffered aqueous solution
R0908
R1881, ≥98% (HPLC)
C19H24O2