Am80 induces neuronal differentiation in a human neuroblastoma NH-12 cell line.
Retinoids including natural vitamin A, its derivatives and synthetic compounds work as transcription factors through the retinoic acid receptors (RAR, RXR). All-trans retinoic acid (ATRA), a family of retinoids, is an internal ligand of RAR and well known as a useful differentiation inducer to treat acute promyelocytic leukemia (APL). ATRA therapy is now established as an initial treatment for APL. Recently, to improve therapeutic potency and reduce adverse effects of ATRA, a novel synthetic selective agonist for RARalpha and beta, Am80, was developed and applied to APL treatment. In this study, we tested whether Am80 was capable of inducing neuronal differentiation in a human neuroblastoma cell line, NH-12 and compared the differentiation effects between Am80 and ATRA. Morphological studies demonstrated that Am80 induced more potent neurite outgrowth and also proved lesser cell toxicity than ATRA. Am80 up-regulated the expression of tropomyosin-related kinase B as well as ATRA. Moreover, Am80 increased the expression of the neuronal marker, growth-associated protein 43. These findings suggest that Am80 induces neuronal differentiation to a greater extent than ATRA and thus may help establishing therapeutic strategies against neuronal degenerative disorders such as Parkinson's disease.
Shiohira
Hideo
H
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Jonan-ku, Fukuoka, Japan.
Kitaoka
Akira
A
Shirasawa
Hiromi
H
Enjoji
Munechika
M
Nakashima
Manabu
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D001565:Benzoates; D019922:GAP-43 Protein; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D014212:Tretinoin