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.