title: 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abstract: MDI 301 is a novel 9-cis retinoic acid derivative in which the terminal carboxylic acid group has been replaced by a picolinate ester.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.affiliation: Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Aslam
authors.forename: Shannon
authors.initials: S
authors.lastname: McClintock
authors.forename: Shazli P
authors.initials: SP
authors.lastname: Khan
authors.forename: Patricia
authors.initials: P
authors.lastname: Perone
authors.forename: Ronald
authors.initials: R
authors.lastname: Allen
authors.forename: Peter D
authors.initials: PD
authors.lastname: Ouillette
authors.forename: Michael K
authors.initials: MK
authors.lastname: Dame
authors.forename: Jason X
authors.initials: JX
authors.lastname: Cheng
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: James
authors.initials: J
authors.lastname: Varani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008819:Mice, Nude; D012176:Retinoids / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D014212:Tretinoin / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D039481:CD11b Antigen; D018821:CD18 Antigens; C488463:MDI 301; D012176:Retinoids; D014212:Tretinoin