Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells

doi:10.3390/antiox8090402

	Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells
	Lu, Xuxiu 1; Geng, Jiajia 1; Zhang, Jinman 1; Miao, Jinlai 2,3; Liu, Ming 1,2,4
刊名	ANTIOXIDANTS
	2019-09
卷号	8 期号:9
关键词	K562 xanthohumol BCR-ABL degradation autophagy caspase
DOI	10.3390/antiox8090402
英文摘要	BCR-ABL oncoprotein drives the initiation, promotion, and progression of chronic myelogenous leukemia (CML). Tyrosine kinase inhibitors are the first choice for CML therapy, however, BCR-ABL mediated drug resistance limits its clinical application and prognosis. A novel promising therapeutic strategy for CML therapy is to degrade BCR-ABL using small molecules. Antioxidant xanthohumol (XN) is a hop-derived prenylated flavonoid with multiple bioactivities. In this study, we showed XN could inhibit the proliferation, induce S phase cell cycle arrest, and stimulate apoptosis in K562 cells. XN degraded BCR-ABL in a concentration- and time-dependent manner, and the involved degradation pathway was caspase activation, while not autophagy induction or ubiquitin proteasome system (UPS) activation. Moreover, we revealed for the first time that XN could inhibit the UPS and autophagy in K562 cells, and the inhibitory effect of XN on autophagy could attenuate imatinib-induced autophagy and enhance the therapeutic efficiency of imatinib in K562 cells. Our present findings identified XN act as a degrader of BCR-ABL in K562 cells, and XN had potential to be developed as an alternate agent for CML therapy.
资助项目	State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University)[CMEMR2019-B05]
WOS关键词	LEUKEMIA-CELLS ; PROTEASOMAL DEGRADATION ; GROWTH-INHIBITION ; MOLECULAR-BIOLOGY ; HUMULUS-LUPULUS ; IN-VITRO ; KAPPA-B ; CANCER ; APOPTOSIS ; KINASE
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Food Science & Technology
语种	英语
出版者	MDPI
WOS记录号	WOS:000487957300067
内容类型	期刊论文
源URL	[http://ir.fio.com.cn:8080/handle/2SI8HI0U/30174]
专题	自然资源部第一海洋研究所
通讯作者	Miao, Jinlai; Liu, Ming
作者单位	1.Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ, Qingdao 266003, Shandong, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266237, Shandong, Peoples R China 3.MNR, Key Lab Marine Bioact Subst, Inst Oceanog 1, Qingdao 266061, Shandong, Peoples R China 4.Guangxi Normal Univ, State Key Lab Chem & Mol Engn Med Resources, Guilin 541001, Peoples R China
推荐引用方式 GB/T 7714	Lu, Xuxiu,Geng, Jiajia,Zhang, Jinman,et al. Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells[J]. ANTIOXIDANTS,2019,8(9).
APA	Lu, Xuxiu,Geng, Jiajia,Zhang, Jinman,Miao, Jinlai,&Liu, Ming.(2019).Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells.ANTIOXIDANTS,8(9).
MLA	Lu, Xuxiu,et al."Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells".ANTIOXIDANTS 8.9(2019).