Activity of MDI-301, a novel synthetic retinoid, in xenografts.
The efficacy of MDI-301, a non-toxic novel synthetic retinoid, was found to be equivalent to the natural 9-cis-retinoic acid (RA) in vitro against estrogen-dependent MCF7 and T47D breast cancer cell lines which express RA receptor (RAR) alpha. Both retinoids also showed similar efficacy against established PC-3 prostate carcinoma xenografts. MCF7 tumor xenografts showed a reduction in tumor growth of 48% without systemic side-effects upon treatment with MDI-301 compared with MCF7 controls. Tumor xenografts derived from MDA-MB-231, an estrogen-independent breast cancer cell line that expresses low levels of RARalpha, were unresponsive. This study demonstrates that MDI-301 is as efficacious as 9-cis-RA against cancer cells with RARalpha, with no signs of toxicity in vivo, making it a potential candidate for cancer therapy.
Appleyard
Virginia C L
VC
Department of Surgery, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
O'Neill
Mary A
MA
Murray
Karen E
KE
Bray
Susan E
SE
Thomson
George
G
Kernohan
Neil M
NM
Varani
James
J
Zhang
Jian
J
Thompson
Alastair M
AM
D000077556:Alitretinoin; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C488463:MDI 301; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D000077556:Alitretinoin; D014212:Tretinoin