Role of Protein Kinase C-iota in Transformed Non-malignant RWPE-1 Cells and Androgen-independent Prostate Carcinoma DU-145 Cells

Overview

Journal Cell Prolif

Date 2009 Feb 27

PMID 19243387

Citations 9

Authors

H Y Win

M Acevedo-Duncan

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Prostate cancer is one of the leading causes of death among men in the USA.

Objective: In this study, we investigated the role of atypical protein kinase C-iota (PKC-iota) in androgen independent prostate DU-145 carcinoma cellscompared to transformed non-malignant prostate RWPE-1 cells.

Materials And Methods: Western blotting and immunoprecipitations demonstrated that PKC-iotaisassociated with cyclin-dependent kinase activating kinase (CAK/Cdk7) in RWPE-1 cells, but not in DU-145 cells.

Results: Treatment of prostate RWPE-1 cells with PKC-iota silencing RNA (siRNA) decreased cell viability,cell-cycle accumulation at G2/M phase, and phosphorylation of Cdk7 and Cdk2. In addition, PKC-iota siRNA treatment caused less phosphorylation ofBad at ser-155, ser-136, and greater Bad/Bcl-xL heterodimerization, leading to apoptosis. In DU-145 cells, PKC-iota was anti-apoptotic and was required for cell survival. Treatment with PKC-iota siRNA blocked increase in cell number, and inhibited G1/S transition by accumulation of cells in G0/G1phase. In addition to cell-cycle arrest, both RWPE-1 and DU-145 cells underwent apoptosis due to mitochondrial dysfunction and apoptosis cascades, such as release of cytochrome c,activation of caspase-7, and poly (ADP-ribose)polymerase (PARP) cleavage.

Conclusion: Our results suggest that PKC-iota is required for cell survival in both transformed non-malignant prostate RWPE-1 cells and androgen-independent malignant prostate DU-145 cells, whereas suppressing PKC-iota lead to apoptosis in DU-145 prostate cells.

Citing Articles

The Dual Roles of the Atypical Protein Kinase Cs in Cancer.

Reina-Campos M, Diaz-Meco M, Moscat J Cancer Cell. 2019; 36(3):218-235.

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Preclinical testing of 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide: a potent protein kinase C-ι inhibitor as a potential prostate carcinoma therapeutic.

Apostolatos A, Apostolatos C, Ratnayake W, Neuger A, Sansil S, Bourgeois M Anticancer Drugs. 2018; 30(1):65-71.

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A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells.

Kim H, Cho S, Heo H, Jeong S, Kim M, Ko K Mar Drugs. 2018; 16(6).

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Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis.

Ratnayake W, Apostolatos A, Ostrov D, Acevedo-Duncan M Int J Oncol. 2017; 51(5):1370-1382.

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Atypical protein kinase C zeta: potential player in cell survival and cell migration of ovarian cancer.

Seto K, Andrulis I PLoS One. 2015; 10(4):e0123528.

PMID: 25874946 PMC: 4397019. DOI: 10.1371/journal.pone.0123528.

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