title: Camptothecin and its analogs reduce amyloid-β production and amyloid-β42-induced IL-1β production.
abstract: Compounds derived from natural products are becoming promising alternative drugs/tools in Alzheimer's disease (AD) therapeutics. From an in-house natural products library, seventeen hits were selected for their inhibitory effect on the production of amyloid-β (Aβ) with IC50 lower than 10 μM without causing obvious toxicity. Among these compounds, camptothecin (CPT) and its analogs showed inhibitory effects on amyloid-β 1-42 (Aβ42) with the IC50 value in the nanomolar range in HEKsw cells and SHSY5Ysw cells. Further studies showed that CPT and its analogs inhibited Aβ42 via a p53 dependent pathway. Meanwhile, CPT and its analogs could also inhibit Aβ42 induced IL-1β production in the THP-1 cells. Taken together, our results indicate that CPT and its analogs would be a promising therapeutic candidates for AD.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Zi-Qi
authors.initials: ZQ
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Gui-Zhong
authors.initials: GZ
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000378:metabolism*; D013058:Mass Spectrometry; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053583:Interleukin-1beta; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D020169:Caspases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D002166:Camptothecin
keywords: Alzheimer's disease; IL-1β; amyloid-β; camptothecin; p53