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Int. J. Mol. Sci. 2016, 17(5), 676; doi:10.3390/ijms17050676

A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway

1,†
,
2,†
,
3,†
,
1
,
1,4,* , 3
,
1,5,* and 1,*
1
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
2
Department of Gastroenterology, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu 610041, China
3
Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
4
Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
5
Department of Urology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Bing Yan
Received: 29 March 2016 / Revised: 21 April 2016 / Accepted: 25 April 2016 / Published: 17 May 2016
(This article belongs to the Collection Bioactive Nanoparticles)
View Full-Text   |   Download PDF [5129 KB, uploaded 19 May 2016]   |  

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. View Full-Text
Keywords: prostate specific membrane-antigen; wogonin; prostate cancer; apoptosis prostate specific membrane-antigen; wogonin; prostate cancer; apoptosis
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Zhang, H.; Liu, X.; Wu, F.; Qin, F.; Feng, P.; Xu, T.; Li, X.; Yang, L. A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway. Int. J. Mol. Sci. 2016, 17, 676.

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