Open AccessTumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine‐specific phospholipase C
Author(s) -
Upham Brad L.,
Bláha Ludek,
Babica Pavel,
Park JoonSuk,
Sovadinova Iva,
Pudrith Charles,
Rummel Alisa M.,
Weis Liliane M.,
Sai Kimie,
Tithof Patti K.,
Gužvić Miodrag,
Vondráček Jan,
Machala Miroslav,
Trosko James E.
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00752.x
Subject(s) - phospholipase c , phosphatidylcholine , phospholipase , protein kinase c , protein kinase a , phosphatidylinositol , kinase , diacylglycerol kinase , microbiology and biotechnology , biochemistry , phospholipase d , biology , chemistry , signal transduction , enzyme , phospholipid , membrane
Inhibition of gap junctional intercellular communication (GJIC) and the activation of intracellular mitogenic pathways are common hallmarks of epithelial derived cancer cells. We previously determined that the 1‐methyl and not the 2‐methyl isomer of anthracene, which are prominent cigarette smoke components, activated extracellular receptor kinase, and inhibited GJIC in WB‐F344 rat liver epithelial cells. Using these same cells, we show that an immediate upstream response to 1‐methylanthracene was a rapid (<1 min) release of arachidonic acid. Inhibition of phosphatidylcholine‐specific phospholipase C prevented the inhibition of GJIC by 1‐methylanthracene. In contrast, inhibition of phosphatidylinositol specific phospholipase C, phospholipase A 2 , diacylglycerol lipase, phospholipase D, protein kinase C, and tyrosine protein kinases had no effect on 1‐methylanthracene‐induced inhibition of GJIC. Inhibition of protein kinase A also prevented inhibition of GJIC by 1‐methylanthracene. Direct measurement of phosphatidylcholine‐specific phospholipase C and sphingomyelinase indicated that only phosphatidylcholine‐specific phospholipase C was activated in response to 1‐methylanthracene, while 2‐methylanthracene had no effect. 1‐methylanthracene also activated p38‐mitogen activated protein kinase; however, like extracellular kinase, its activation was not involved in 1‐methylanthracene‐induced regulation of GJIC, and this activation was independent of phosphatidylcholine‐specific phospholipase C. Although mitogen activated protein kinases were activated, Western blot analyzes indicated no change in connexin43 phosphorylation status. Our results indicate that phosphatidylcholine‐specific phospholipase C is an important enzyme in the induction of a tumorigenic phenotype, namely the inhibition of GJIC; whereas mitogen activated protein kinases triggered in response to 1‐methylanthracene, were not involved in the deregulation of GJIC. ( Cancer Sci 2008; 99: 696–705)