PMID- 27196894 OWN - NLM STAT- MEDLINE DCOM- 20170316 LR - 20181202 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 5 DP - 2016 May 17 TI - A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway. LID - 10.3390/ijms17050676 [doi] LID - 676 AB - 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 zeta 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. FAU - Zhang, Hailong AU - Zhang H AD - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. hailong6891@163.com. FAU - Liu, Xiaogang AU - Liu X AD - 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. FAU - Wu, Fengbo AU - Wu F AD - Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. wufengbo_@163.com. FAU - Qin, Feifei AU - Qin F AD - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. sklb_qff@sina.com. FAU - Feng, Ping AU - Feng P AD - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com. AD - Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com. FAU - Xu, Ting AU - Xu T AD - Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xt_wch@163.com. FAU - Li, Xiang AU - Li X AD - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn. AD - Department of Urology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn. FAU - Yang, Li AU - Yang L AD - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. yl.tracy73@gmail.com. LA - eng PT - Journal Article DEP - 20160517 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antigens, Surface) RN - 0 (Flavanones) RN - 0 (Micelles) RN - 0 (Pentanoic Acids) RN - 0 (polyethylene glycol-cholesterol) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.4.17.21 (FOLH1 protein, human) RN - EC 3.4.17.21 (Glutamate Carboxypeptidase II) RN - POK93PO28W (wogonin) SB - IM MH - Antigens, Surface MH - Apoptosis MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cholesterol/analogs & derivatives/chemistry MH - Flavanones/chemistry/*pharmacology MH - Gene Expression Regulation, Neoplastic/drug effects MH - Glutamate Carboxypeptidase II/*antagonists & inhibitors MH - Humans MH - Male MH - Micelles MH - Molecular Targeted Therapy/*methods MH - Pentanoic Acids/chemistry MH - Polyethylene Glycols/chemistry MH - Prostatic Neoplasms/drug therapy/*metabolism MH - Signal Transduction/drug effects PMC - PMC4881502 OTO - NOTNLM OT - apoptosis OT - prostate cancer OT - prostate specific membrane-antigen OT - wogonin EDAT- 2016/05/20 06:00 MHDA- 2017/03/17 06:00 PMCR- 2016/05/01 CRDT- 2016/05/20 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/04/21 00:00 [revised] PHST- 2016/04/25 00:00 [accepted] PHST- 2016/05/20 06:00 [entrez] PHST- 2016/05/20 06:00 [pubmed] PHST- 2017/03/17 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - ijms17050676 [pii] AID - ijms-17-00676 [pii] AID - 10.3390/ijms17050676 [doi] PST - epublish SO - Int J Mol Sci. 2016 May 17;17(5):676. doi: 10.3390/ijms17050676.