Open AccessInhibitory Effect of 8‐Chloro‐cyclic Adenosine 3′,5′‐Monophosphate on Cell Growth of Gastric Carcinoma Cell Lines
Author(s) -
Takanashi Atsushi,
Yasui Wataru,
Yoshida Kazuhiro,
Yokozaki Hiroshi,
Saito Daizo,
Abe Kaoru,
Urakami Kenichi,
Mild Keizaburo,
Tahara Eiichi
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01849.x
Subject(s) - protein kinase a , cyclic adenosine monophosphate , biology , endocrinology , cell culture , medicine , cell growth , hras , microbiology and biotechnology , receptor , kinase , biochemistry , gene , mutation , genetics , kras
A cAMP analogue, 8‐chloro‐cAMP (8‐Cl‐cAMP), selectively binds to site 1 receptor of type II regulatory subunit (RII) of cAMP‐dependent protein kinase. The effects of 8‐Cl‐cAMP on human gastric carcinoma cell lines were studied. Twenty μM 8‐CI‐cAMP clearly inhibited cell growth in six cell lines (TMK‐1, KATO‐III, MKN‐7, ‐28, ‐45, and ‐74) but not in MKN‐1. Cell population in the G 1 phase was increased in KATO III cells, which were most responsive to 8‐Cl‐cAMP, while cell cycle progression in TMK‐1 and MKN‐1 cells was apparently not influenced by 8‐Cl‐cAMP. The various changes induced by 8‐Cl‐cAMP were further analyzed in TMK‐1 cells. Decrease of type I regulatory subunit (RI) of cAMP‐dependent protein kinase and translocation of RII from cytosol to nucleus were induced by 8‐Cl‐cAMP treatment. 8‐CI‐cAMP increased the level of cAMP‐response element (CRE) binding protein in addition to inducing FOS mRNA, whose promoter contains CRE. 8‐Cl‐cAMP decreased the expression of mRNA for transforming growth factor‐α (TGF‐α), while the expression of epidermal growth factor receptor was not changed. Expression of HRAS and MYC mRNAs was slightly increased, whereas the amounts of HRAS and MYC proteins remained unchanged. Our results overall suggest that 8‐Cl‐cAMP might be a useful tool for antitnmor therapy of gastric cancers and that cell growth inhibition by 8‐Cl‐cAMP might account for the decrease of TGF‐α expression by tumor cells.