國家衛生研究院 NHRI:Item 3990099045/12020

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12020

Title:	Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3-induced mitophagy
Authors:	Lee, WJ;Chen, LC;Lin, JH;Cheng, TC;Kuo, CC;Wu, CH;Chang, HW;Tu, SH;Ho, YS
Contributors:	Institute of Biotechnology and Pharmaceutical Research;NHRI Graduate Student Program
Abstract:	Neuroblastoma is the second most common pediatric malignancy and has a high rate of spontaneous remission. Uncovering the mechanisms underlying neuroblastoma cell differentiation is critical for therapeutic purposes. A neuroblastoma cell line (N2a) treated with either serum withdrawal (<2.5%) or melatonin (>0.1 nmol/L) for 24 hours was used as a cell differentiation research model. Interestingly, the hyaluronan synthase 3 (HAS3) protein was induced in differentiated N2a cells. N2a-allografted nude mice received an intraperitoneal injection of melatonin (40 or 80 mg/kg/day for 3 weeks). The mean tumor volume in mice treated with 80 mg/kg melatonin was smaller than that in PBS-treated mice (1416.3 and 3041.3 mm(3), respectively, difference = 1625 mm(3), P = 0.0003, n = 7 per group). Compared with the vector control group, N2a cells with forced HAS3 overexpression showed significantly increased neuron length (P = 0.00082) and neurite outgrowth (*P = 0.00059). Intracellular changes in autophagy, including distorted mitochondria with abnormal circular inner membranes, were detected by transmission electron microscopy (TEM). Our study demonstrated that HAS3-mediated signaling activated by physiological concentrations of melatonin (>0.1 nmol/L) triggered significant N2a cell differentiation. These results provide molecular data with potential clinical relevance for therapeutic drug development.
Date:	2019-08
Relation:	Cancer Medicine. 2019 Aug;8(10):4821-4835.
Link to:	http://dx.doi.org/10.1002/cam4.2389
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-7634&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000474088800001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85071284753
Appears in Collections:	[Ching-Chuan Kuo] Periodical Articles [Others] Periodical Articles

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