Activity of MDI-301, a novel synthetic retinoid, in xenografts.

Abstract

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.

• Authors: Virginia C L Appleyard, Mary A O'Neill, Karen E Murray, Susan E Bray, George Thomson, Neil M Kernohan, James Varani, Jian Zhang, Alastair M Thompson
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 15 Issue 10 Pg. 991-6 (Nov 2004) ISSN: 0959-4973 [Print] England
• PMID: 15514569 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• MDI 301
• RARA protein, human
• Rara protein, mouse
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Retinoids
• Alitretinoin
• Tretinoin

Topics

• Alitretinoin
• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• Male
• Mice
• Mice, Nude
• Prostatic Neoplasms
• Receptors, Retinoic Acid (biosynthesis)
• Retinoic Acid Receptor alpha
• Retinoids (pharmacology)
• Tretinoin (pharmacology)
• Xenograft Model Antitumor Assays