title: Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells.
abstract: One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
authors.forename: Johana
authors.initials: J
authors.lastname: Tello Velasquez
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Watts
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Todorovic
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
authors.forename: Lynnmaria
authors.initials: L
authors.lastname: Nazareth
authors.affiliation: Nature Communications, New York, New York, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Pastrana
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Diaz-Nido
authors.affiliation: Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Filip
authors.initials: F
authors.lastname: Lim
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
authors.forename: Jenny A K
authors.initials: JA
authors.lastname: Ekberg
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: St John
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D063990:Gene Ontology; D008297:Male; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009830:Olfactory Bulb / Q000166:cytology*; D009831:Olfactory Mucosa / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003474:Curcumin