Abstract
Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ1, and PAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC3, LAMP1, and ATG5, were upregulated along with the expression of neural genes. The inhibition of autophagy by chloroquine suppressed both autophagy and neural differentiation, highlighting the positive role of autophagy during neural differentiation. This autophagy-mediated neural differentiation of curcumin was found to be an ROS-dependent manner; curcumin induced ROS generation and suppressed antioxidant gene expression. Altogether, this study proposed the neural-inducing activity of curcumin via the regulation of autophagy within NTERA2 cells and underscored the health beneficial effects of curcumin for neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.
Highlights
The embryonal carcinoma stem cells, named NTERA2 cells, are derived from a human testicular cancer and are able to differentiate into functional postmitotic neurons and other cell types of neural lineages [1,2,3]
Curcumin possesses multiple biological and pharmacological properties, and neurogenic activity of curcumin became an area of interest [25, 26]
Besides neural cell proliferation [22, 27] and neuroprotection [28, 29], curcumin was found to increase the rate of neural differentiation from neural stem cells via the activation of the classical WNT pathway [27]
Summary
The embryonal carcinoma stem cells, named NTERA2 cells, are derived from a human testicular cancer and are able to differentiate into functional postmitotic neurons and other cell types of neural lineages [1,2,3]. NTERA2 cells exhibit comparable differentiation potential with human embryonic stem cells and could be used to study the early stages of human neurogenesis [4]. NTERA2 cells were differentiated into neurons, which resembled the vertebrate neurogenesis [5,6,7,8]. The morphological characteristics of neurons could be observed after 10-14 days of the exposure of NTERA2 to retinoic acid. Oligodendrocyte lineage, such as NG2 and GalC-positive cells, could be generated from the differentiation of NTERA-2 cells [13]. NTERA2 cells are considered as the feasible model for studying mechanisms of neural differentiation of the nervous system [6]
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