Carcinogenesis, Vol 19, 827-832, Copyright © 1998 by Oxford University Press
Z Ren and MN Gould
Monoterpenes have been shown to both prevent and treat mammary cancer in
animal models and are currently in clinical testing in advanced cancer
patients. In this study, we investigated a biochemical modulation
associated with the antitumor activity of monoterpenes, the inhibition of
protein isoprenylation in monoterpene chemoprevention target tissue, i.e.
the in situ mammary gland epithelial cells. We first developed a new
methodology that for the first time permitted the study of protein
isoprenylation and other products in the mevalonate pathway in in situ
mammary cells. Using this approach, we found that chronically feeding rats
with an anticancer dose of perillyl alcohol resulted in a 22% inhibition of
coenzyme Q synthesis and a 19% inhibition of small G protein isoprenylation
in mammary gland epithelial cells in situ. The greatest inhibition of small
G protein isoprenylation observed was the 28% inhibition of isoprenylation
of RhoA by type I geranylgeranyl protein transferase (GGPTase). Given that
some substrates of type I GGPTase, such as RhoA and Rac1, have transforming
properties, the possibility that the inhibition of type I GGPTase will
change the cellular location and functionality of these proteins and thus
contribute to the chemoprevention activity of monoterpenes, is discussed.
ARTICLES
Modulation of small G protein isoprenylation by anticancer monoterpenes in in situ mammary gland epithelial cells
University of Wisconsin-Madison, Department of Human Oncology, 53792, USA.
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