title: A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway.
abstract: Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self-assembling method, which produced stable particle size and ζ potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG's effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. hailong6891@163.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu 610041, China. lxg_sph@163.com.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. wufengbo_@163.com.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. sklb_qff@sina.com.
authors.forename: Feifei
authors.initials: F
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com.|Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xt_wch@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn.|Department of Urology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. yl.tracy73@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000954:Antigens, Surface; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008823:Micelles; D058990:Molecular Targeted Therapy / Q000379:methods*; D010421:Pentanoic Acids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000954:Antigens, Surface; D044950:Flavanones; D008823:Micelles; D010421:Pentanoic Acids; C118255:polyethylene glycol-cholesterol; D011092:Polyethylene Glycols; D002784:Cholesterol; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; C085514:wogonin
keywords: apoptosis; prostate cancer; prostate specific membrane-antigen; wogonin