000			02343nam a2200301Ia 4500
003			MX-MdCICY
005			20250625162448.0
040			_cCICY
090			_aB-20401
245	1	0	_aInvestigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics
490	0		_vActa Pharmacologica Sinica, 44, p.1701-1711, 2023
520	3		_aEriocalyxin B (EB), 17-hydroxy-jolkinolide B (HJB), parthenolide (PN), xanthatin (XT)and andrographolide (AG)are terpenoid natural products with a variety of promising antitumor activities, which commonly bear electrophilic groups (?,?-unsaturated carbonyl groups and/or epoxides)capable of covalently modifying protein cysteine residues. However, their direct targets and underlying molecular mechanisms are still largely unclear, which limits the development of these compounds. In this study, we integrated activity-based protein profiling (ABPP)and quantitative proteomics approach to systematically characterize the covalent targets of these natural products and their involved cellular pathways. We first demonstrated the anti-proliferation activities of these five compounds in triple-negative breast cancer cell MDA-MB-231. Tandem mass tag (TMT)-based quantitative proteomics showed all five compounds commonly affected the ubiquitin mediated proteolysis pathways. ABPP platform identified the preferentially modified targets of EB and PN, two natural products with high anti-proliferation activity. Biochemical experiments showed that PN inhibited the cell proliferation through targeting ubiquitin carboxyl-terminal hydrolase 10 (USP10). Together, this study uncovered the covalently modified targets of these natural products and potential molecular mechanisms of their antitumor activities.
650	1	4	_aNATURAL PRODUCTS
650	1	4	_aPROTEOMICS
650	1	4	_aABPP
650	1	4	_aERIOCALYXIN B
650	1	4	_aPARTHENOLIDE
700	1	2	_aZhao, W. S.
700	1	2	_aChen, K. F.
700	1	2	_aLiu, M.
700	1	2	_aJia, X. L.
700	1	2	_aHuang, Y. Q.
700	1	2	_aHao, B. B.
700	1	2	_aTan, M. J.
856	4	0	_uhttps://drive.google.com/file/d/1vfmWhE20oAretUfk_-8MpNMCmlk2z-JN/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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