In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. A63-A63
Abstract:
Dysregulation of the PI3K-AKT & mTOR pathway by (mutation and/or) deletion of tumor suppressor gene PTEN frequently occurs in human prostate cancer and is therefore considered to be attractive molecule as therapeutic targets. Here, we investigated the antitumor effect of NVP-BEZ235 in human prostate cancer cells dependent on PTEN genotype. In this setting, NVP-BEZ235 induced cell death in the PTEN-independent manner. However, NVP-BEZ235 selectively induced apoptotic cell death in prostate cancer cells presenting wild-type PTEN, DU145, but not in cells with deletion of PTEN, PC3. Treatment with NVP-BEZ235 resulted in autophagic cell death in PC3 cells with PTEN loss of function. Consistently, NVP-BEZ235 treatment did not result in the cleavage of caspase-3 and was link to active LC3-I/II as an indicator of autophagic cell death process, suggesting an alternate route for induction of cell death after exposure to NVP-BEZ235 in PTEN-null prostate cancer cells. These results suggest that PTEN/PI3K/Akt pathways are critical for prostate cancer survival and targeting PI3K signaling by NVP-BEZ235 may be beneficial in prostate cancer independent on PTEN genotype. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A63. Citation Format: Jeong Eun Kim, Seoung-Woo Hong, Jae-Sik Shin, Jai-Hee Moon, Ye-Seul Kim, Kyu-pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Dong-Hoon Jin, Tae Won Kim. NVP-BEZ235, a dual PI3K/mTOR inhibitor, elicits an alternate route for induction of cell death in PTEN null prostate cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A63.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-13-A63
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2062135-8
SSG:
12
