Stimulation of protein kinase C-dependent and -independent signaling pathways by bistratene A in intestinal epithelial cells

Frey, Mark R., Leontieva, Olga, Watters, Dianne J. and Black, Jennifer D. (2001) Stimulation of protein kinase C-dependent and -independent signaling pathways by bistratene A in intestinal epithelial cells. Biochemical Pharmacology, 61 9: 1093-1100. doi:10.1016/S0006-2952(01)00596-2

Author Frey, Mark R.
Leontieva, Olga
Watters, Dianne J.
Black, Jennifer D.
Title Stimulation of protein kinase C-dependent and -independent signaling pathways by bistratene A in intestinal epithelial cells
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 2001
Sub-type Article (original research)
DOI 10.1016/S0006-2952(01)00596-2
Volume 61
Issue 9
Start page 1093
End page 1100
Total pages 8
Editor Alan C. Sartorelli
Jacques E. Gielen
Place of publication Oxford UK
Publisher Pergamon-Elsevier Science Ltd
Collection year 2001
Language eng
Subject C1
270106 Cell Development (incl. Cell Division and Apoptosis)
730108 Cancer and related disorders
Abstract The marine toxin bistratene A (BisA) potently induces cytostasis and differentiation in a variety of systems. Evidence that BisA is a selective activator of protein kinase C (PKC) delta implicates PKC delta signaling in the negative growth-regulatory effects of this agent. The current study further investigates the signaling pathways activated by BisA by comparing its effects with those of the PKC agonist phorbol 12-myristate 13-acetate (PMA) in the IEC-18 intestinal crypt cell line. Both BisA and PMA induced cell cycle arrest in these cells, albeit with different kinetics. While BisA produced sustained cell cycle arrest in G(o)/G(1) and G(2)/M, the effects of PMA were transient and involved mainly a G(o)/G(1), blockade. BisA also produced apoptosis in a proportion of the population, an effect not seen with PMA. Both agents induced membrane translocation/activation of PKC, with BisA translocating only PKC delta and PMA translocating PKC alpha, delta, and epsilon in these cells. Notably, while depletion of PKC alpha, delta, and epsilon abrogated the cell cycle-specific effects of PMA in IEC-18 cells, the absence of these PKC isozymes failed to inhibit BisA-induced G(o)/G(1), and G(2)/M arrest or apoptosis. The cell cycle inhibitory and apoptotic effects of BisA, therefore, appear to be PKC-independent in IEG-18 cells. On the other hand, BisA and PMA both promoted PKC-dependent activation of Erk 1 and 2 in this system. Thus, intestinal epithelial cells respond to BisA through activation of at least two signaling pathways: a PKC delta -dependent pathway, which leads to activation of mitogen-activated protein kinase and possibly cytostasis in the appropriate context, and a PKC-independent pathway, which induces both cell cycle arrest in G(o)/G(1) and G(2)/M and apoptosis through as yet unknown mechanisms. (C) 2001 Elsevier Science Inc. All rights reserved.
Keyword Pharmacology & Pharmacy
Bistratene A
Protein Kinase C
Cell Cycle
Signal Transduction
Intestinal Epithelial Cells
Mitogen-activated Protein Kinase
Phorbol Ester
Proteolytic Activation
Cycle Arrest
Hl-60 Cells
Hl60 Cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Tue, 14 Aug 2007, 15:53:19 EST