A Reitmair

A Torriglia

AE Lewis

AN Fanjul

CM Bunce

D Lohnes

D Lukovic

D M A Wallace

D-L Shurland

DM Peehl

E Duprez

ES Yang

FJ Lopez-Hernandez

FJ Piedrafita

G Brown

IS Mathiasen

J Zhu

JA Fontana

K Wen

KA Moffat

KR You

KW Kelly

L A Hammond

L Altucci

L I Atangan

L Yang

LA Hammond

LY Li

M Enari

M Gao

M Ismail

M Shalev

MA Ortiz

MJ Campbell

N Hail

N Oridate

R A S Chandraratna

R Bird

R G Keedwell

R Sugibayashi

RG Keedwell

RK Spanjaard

RP Singh

RS DiPaolo

RS Kirby

S Qin

S Salvioli

S Wu

S-Y Sun

SH Landis

SR Chinni

T Lufkin

TR Brietman

W Ding

W Gorczyca

WF Holmes

X-P Lu

X-Y Zhang

Y Li

Y Zhao

Z-M Shao

English

PubMed

Screening of synthetic retinoids for activity against prostate carcinoma cell lines has identified antagonists of retinoic acid receptors (RARs) as potent growth inhibitors ( Hammond et al, 2001, Br J Cancer 85, 453 - 462). Here we report that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310) abolished growth of prostate carcinoma cells from 14 out of 14 patients, with half-maximal inhibition between 200 and 800 nM. It had similar effects (at similar to250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3. AGN194310 inhibited the growth of normal prostate epithelium cells less potently, by 50% at similar to1 muM. The growth of tumour cells was also inhibited more than that of normal cells when RARbeta together with RARgamma, but not RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310 arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis was caspase-independent: caspases were neither cleaved nor activated, and DNA fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability of AGN 194310 to induce apoptosis of prostate cancer cells and its differential effect on malignant and normal prostate epithelial cells suggests that this compound may be useful in the treatment of prostate cancer

Keedwell, Richard

Zhao, Y

Hammond, Lisette

Qin, S

Atangan, LI

Shurland, D-L

Wallace, DMA

Bird, R

Reitmair, A

Chandraratna, RAS

Brown, Geoffrey

University of Birmingham Research Portal

An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium

Crossref

Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer 85: 453–462 Holmes WF, Soprano DR, Soprano KJ

High postnatal lethality and testis degeneration in retinoic acid receptor a mutant mice.

Protein kinase C inhibition induces DNA fragmentation in COLO 205 cells which is blocked by cysteine protease inhibition but not mediated through caspase 3. Exp Cell Res 289: 1–10

Sythetic retinoid CD437 promotes rapid apoptosis in malignant human epidermal keratinocytes and G1 arrest in their normal counterparts.

The promise of retinoids to fight against cancer.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2409843

An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium

Abstract

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University of Birmingham Research Portal

Crossref

University of Birmingham Research Portal