Natural Product Albiziabioside A Conjugated with Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate To Induce Apoptosis-Ferroptosis-M2-TAMs Polarization for Combined Cancer Therapy

doi:10.1021/acs.jmedchem.9b00644

	Natural Product Albiziabioside A Conjugated with Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate To Induce Apoptosis-Ferroptosis-M2-TAMs Polarization for Combined Cancer Therapy
	Wei, Gaofei 3,4; Sung, Jiahong 2; Luan, Weijing 1,3; Hou, Zhuang 3; Wang, Shuai 3; Cui, Shanshan 3; Cheng, Maosheng 3; Liu, Yang 3
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2019-10-10
卷号	62 期号:19 页码:8760-8772
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.9b00644
通讯作者	Wei, Gaofei(weigf0605@163.com) ; Cheng, Maosheng(mscheng@syphu.edu.cn) ; Liu, Yang(y.liu@syphu.edu.cn)
英文摘要	The reprogramming of energy metabolism is considered to be one of the main characteristics of cancer. The development of therapeutic agents targeting glycolysis to alter aberrant glucose metabolism and restore oxidative phosphorylation has emerged as an effective approach for cancer therapy. In this way, we have developed a conjugate AlbA-DCA, which can induce a marked increase in intracellular ROS and alleviate the accumulation of lactic acid in TME. Meanwhile, AlbA-DCA selectively kills cancer cells and exhibits an excellent synergistic effect. Mechanism studies confirm that AlbA-DCA can induce apoptosis and ferroptosis. We also confirm that AlbA-DCA can remold the tumor immunosuppression microenvironment via eliminating M2-TAMs to inhibit both primary and distal tumor progression in a dual-4T1 tumor model in female BALB/c mice. As a result, rational design of natural saponin and PDK inhibitor to induce apoptosis-ferroptosis-M2-TAMs polarization for enhanced cancer therapy is a promising strategy, thus providing a new idea for cancer therapy.
资助项目	National Natural Science Foundation of China[81703335] ; National Natural Science Foundation of China[81703599] ; National Natural Science Foundation of China[81473087] ; Natural Science Foundation of Guangdong[2017A030313069] ; Medical Research Foundation of Guangdong[A2017114] ; Program for Liaoning Innovative Talents in University[LR2017043] ; Career Development Support Plan for Young and Middleaged Teachers in Shenyang Pharmaceutical University[ZQN2016005]
WOS关键词	TUMOR-ASSOCIATED MACROPHAGES ; LACTIC-ACID ; FERROPTOSIS ; APOPTOSIS ; DERIVATIVES ; DYSFUNCTION ; METABOLISM ; REVERSAL ; CELLS ; IRON
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000490355000006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282590]
专题	中国科学院上海药物研究所
通讯作者	Wei, Gaofei; Cheng, Maosheng; Liu, Yang
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, Yantai Branch, Yantai 264000, Peoples R China 2.Keck Grad Inst, Sch Pharm & Hlth Sci, Dept Biopharmaceut Sci, Claremont, CA 91711 USA 3.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Liaoning, Peoples R China 4.Northwestern Polytech Univ, Inst Med Res, Xian 710072, Shaanxi, Peoples R China
推荐引用方式 GB/T 7714	Wei, Gaofei,Sung, Jiahong,Luan, Weijing,et al. Natural Product Albiziabioside A Conjugated with Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate To Induce Apoptosis-Ferroptosis-M2-TAMs Polarization for Combined Cancer Therapy[J]. JOURNAL OF MEDICINAL CHEMISTRY,2019,62(19):8760-8772.
APA	Wei, Gaofei.,Sung, Jiahong.,Luan, Weijing.,Hou, Zhuang.,Wang, Shuai.,...&Liu, Yang.(2019).Natural Product Albiziabioside A Conjugated with Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate To Induce Apoptosis-Ferroptosis-M2-TAMs Polarization for Combined Cancer Therapy.JOURNAL OF MEDICINAL CHEMISTRY,62(19),8760-8772.
MLA	Wei, Gaofei,et al."Natural Product Albiziabioside A Conjugated with Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate To Induce Apoptosis-Ferroptosis-M2-TAMs Polarization for Combined Cancer Therapy".JOURNAL OF MEDICINAL CHEMISTRY 62.19(2019):8760-8772.