Selective Activation of ZAK beta Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation

doi:10.3390/ijms21093366

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24908

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24908

Title:	Selective Activation of ZAK beta Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation
Authors:	Fu, CY;Lay, IS;Shibu, MA;Tseng, YS;Kuo, WW;Yang, JJ;Wang, TF;Mahalakshmi, B;Yeh, YL;Huang, CY
Keywords:	osteosarcoma;3-Hydroxy-2-phenylchromone;ZAK beta;apoptosis
Date:	2020
Issue Date:	2022-08-09T08:09:57Z (UTC)
Publisher:	MDPI
Abstract:	Although various advancements in radical surgery and neoadjuvant chemotherapy have been developed in treating osteosarcoma (OS), their clinical prognosis remains poor. A synthetic chemical compound, 3-hydroxylflavone, that is reported to regulate ROS production is known to inhibit human bone osteosarcoma cells. However, its role and mechanism in human OS cells remains unclear. In this study, we have determined the potential of 3-Hydroxy-2-phenylchromone (3-HF) against OS using human osteosarcoma (HOS) cells. Our previous studies showed that Zipper sterile-alpha-motif kinase (ZAK), a kinase member of the MAP3K family, was involved in various cellular events such as cell proliferation and cell apoptosis, and encoded two transcriptional variants, ZAK alpha and beta. In this study, we show that 3-HF induces the expression of ZAK and thereby enhances cellular apoptosis. Using gain of function and loss of function studies, we have demonstrated that ZAK activation by 3-HF in OS cells is confined to a ZAK beta form that presumably plays a leading role in triggering ZAK alpha expression, resulting in an aggravated cancer apoptosis. Our results also validate ZAK beta as the predominant form of ZAK to drive the anticancer mechanism in HOS cells.
URI:	http://dx.doi.org/10.3390/ijms21093366 https://www.webofscience.com/wos/woscc/full-record/WOS:000535581700337 https://ir.csmu.edu.tw:8080/handle/310902500/24908
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2020 ,v21 ,issue 9
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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