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Int J Mol Sci. 2016 May 17;17(5). pii: E676. 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.

Zhang H1, Liu X2, Wu F3, Qin F4, Feng P5,6, Xu T7, Li X8,9, Yang L10.

Author information

1
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. hailong6891@163.com.
2
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.
3
Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. wufengbo_@163.com.
4
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. sklb_qff@sina.com.
5
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com.
6
Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. pfyq@yahoo.com.
7
Department of Pharmacy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xt_wch@163.com.
8
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn.
9
Department of Urology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. xiangli.87@scu.edu.cn.
10
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. yl.tracy73@gmail.com.

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.

KEYWORDS:

apoptosis; prostate cancer; prostate specific membrane-antigen; wogonin

PMID:
27196894
PMCID:
PMC4881502
DOI:
10.3390/ijms17050676
[Indexed for MEDLINE]
Free PMC Article

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