Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness

Title
Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness
Author
서혜원
Keywords
Pyrrolo[2,3-d]pyrimidine; Prostate cancer; Apoptosis; Autophagy; p21(Cip1); Androgen
Issue Date
2016-02
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v. 26, No. 4, Page. 1130-1135
Abstract
Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d] pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaPC4-2 (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 mu M compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaPC4-2 cells was possible by intensive cell treatment with compound 5 (9 mu M, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 mu M compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells. (C) 2016 Elsevier Ltd. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0960894X16300579http://hdl.handle.net/20.500.11754/49697
ISSN
0960-894X; 1464-3405
DOI
10.1016/j.bmcl.2016.01.057
Appears in Collections:
RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY(약학기술연구소) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE