MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy.

Abstract

MDI 301 is a novel 9-cis retinoic acid derivative in which the terminal carboxylic acid group has been replaced by a picolinate ester. MDI 301, a retinoic acid receptor-α - agonist, suppressed the growth of several human myeloid leukemia cell lines (HL60, NB4, OCI-M2, and K562) in vitro and induced cell-substrate adhesion in conjunction with upregulation of CD11b. Tumor growth in HL60-injected athymic nude mice was reduced. In vitro, MDI 301 was comparable to all-trans retinoic acid (ATRA) whereas in vivo, MDI 301 was slightly more efficacious than ATRA. Most importantly, unlike what was found with ATRA treatment, MDI 301 did not induce a cytokine response in the treated animals and the severe inflammatory changes and systemic toxicity seen with ATRA did not occur. A retinoid with these characteristics might be valuable in the treatment of promyelocytic leukemia, or, perhaps, other forms of myeloid leukemia.

• Authors: Muhammad N Aslam, Shannon McClintock, Shazli P Khan, Patricia Perone, Ronald Allen, Peter D Ouillette, Michael K Dame, Jason X Cheng, Steven L Kunkel, James Varani
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 26 Issue 7 Pg. 763-73 (Aug 2015) ISSN: 1473-5741 [Electronic] England
• PMID: 26010252 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CD11b Antigen
• CD18 Antigens
• MDI 301
• Retinoids
• Tretinoin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use, toxicity)
• CD11b Antigen (metabolism)
• CD18 Antigens (metabolism)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, pathology)
• Mice, Nude
• Retinoids (pharmacology, therapeutic use, toxicity)
• Tretinoin (pharmacology, toxicity)