Inhibition of cytokinesis and akt phosphorylation by chaetoglobosin K in ras-transformed epithelial cells

Abstract

Our results demonstrate that ChK inhibits Akt kinase phosphorylation and cytokinesis in ras-transformed cells, which likely contribute to its ability to inhibit tumorigenic growth.

Protective Effect of the Natural Product, Chaetoglobosin K, on Lindane- and Dieldrin-induced Changes in Astroglia: Identification of Activated Signaling Pathways

“…We previously reported that ChK down-regulates the Akt pathway in ras-transformed epithelial cells (5). In those studies, 2-10 mM ChK induced decreased Akt phosphorylation at 4-72 h treatment times.…”

“…Chaetoglobosin K (ChK) is a natural product compound isolated from Diplodia macrospora (3) that has previously been shown to suppress the tumorigenic phenotype in transformed fibroblasts (4), and inhibit growth of ras-transformed liver epithelial cells (5). It has also been shown to prevent inhibitory effects of tumor promoting organochlorine compounds on gap junction-mediated cell-cell communication in astroglial and epithelial cells (6).…”

A Cell-Cell Communication Marker for Identifying Targeted Tumor Therapies

“…This method was slightly modified from a previously published method [9]. Briefly, cells grown in 35 mm dishes were washed once with PBS containing 0.5 mM CaCl 2 , 0.5 mM MgCl 2 (Ca 2+/ Mg 2+ PBS, to prevent cell detachment) and twice in PBS.…”

“…Cell proteins were extracted using a 2% SDS total protein extraction method [9]. Protein in each sample was quantified using the Bio-Rad DC protein assay.…”

“…Thus, it is critical to understand the intercellular signaling pathways that are dysfunctional, and how new anti-tumor compounds are able to increase gap junction-mediated cell-cell communication between tumor cells and suppress their tumorigenic characteristics. Chaetoglobosin K (ChK), a bioactive natural product [8], has been shown to suppress the tumorigenic phenotype in ras -transformed epithelial cells, to prevent tumor promoter-induced inhibition of intercellular communication, and to modulate the PI-3/Akt kinase pathway [9]. 4-phenyl-3-butenoic acid (PBA) is an experimental compound that has been shown to up-regulate cell-cell communication, reverse the transformed phenotype [10], and preferentially modulate the p38 MAPK pathway [11].…”