Affiliations: Department of Clinical and Biological Sciences,
University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy | National Research Council, Italy
Note: [] Address for correspondence: Dr Fiorella Biasi, Department of
Clinical and Biological Sciences, San Luigi Hospital, 10043 Orbassano (Torino),
Italy. Tel.: +39 011 6705434; Fax: +39 011 6705424; E-mail:
fiorella.biasi@unito.it
Abstract: 4-Hydroxynonenal (HNE) has been demonstrated to exert its
antiproliferative effect by up-regulating the c-Jun-N-terminal kinase (JNK), a
member of the mitogen-activated protein kinase family (MAPKs). Transforming
growth factor-β1 (TGF-β1) is the major negative regulatory factor in
controlling cell proliferation, and Smads are its intracellular transducers.
Recent data on human colon adenocarcinoma has shown a low HNE content
paralleled by a marked alteration of TGF-β1 levels within the tumor mass.
The two events appear related because of the demonstrated marked ability of HNE
to up-regulate expression and synthesis of TGF-β1; the combined decreases
of HNE and TGF-β1 found in cancer cells provide a favorable condition for
neoplastic progression. Furthermore, HNE is likely able to interact with the
cytokine to enhance apoptosis and increase intracellular reactive oxygen
species (ROS) formation in the CaCo-2 colon carcinoma cell line. The probable mechanism whereby HNE and TGF-β1 interact to
induce apoptosis is through cross-talk between the main signaling pathways of
the two molecules (JNK and Smads), and the observed ROS production might only
contribute to amplifying the apoptotic pathways. The network between the two
signaling pathways here involved is now under investigation.
