Abstract
Sodium selenite administered to normal and hepatoma (HA)-bearing mice sc (2 mg/kg) or ip (1 mg/kg) led to a significant increase in cyclic AMP (cAMP) level and a decrease in cAMP phosphodiesterase (PDE) activity in HA cells. In contrast, in tumor host liver and normal liver the cAMP level was reduced, and the PDE activity was slightly elevated, whereas the cAMP adenylate cyclase (AC) was little affected by Na2SeO3, if at all. These results imply that selenite-induced changes in PDE activity play a decisive role in regulating intracellular cAMP level. Kinetic studies revealed that there were different forms of PDE. TheK m value of PDE isozymes in normal liver and host liver were identical, but differed from those of HA. It seems likely that the selective responsiveness of PDE to selenite may be related to the difference in PDE isozyme patterns. Addition of DBcAMP to the culture medium resulted in an inhibition of3H-thymidine incorporation into hepatoma cells, indicating that the inhibition of HA cell proliferation was cAMP-mediated. Thus, selenium has been shown to exert a selective effect on cAMP metabolism of hepatoma cells, which may account for its inhibitory effects on cancer cells.
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References
R. J. Shamberger,J. Natl. Cancer Inst. 44, 931 (1970).
A. C. Griffin and M. M. Jacobs,Cancer Lett. 3, 177 (1977).
M. M. Jacobs, B. Jansson, and A. C. Griffin,Cancer Lett. 2, 133 (1977).
H. J. Thompson and P. J. Becci,J. Natl. Cancer Inst. 65, 1229 (1980).
G. N. Schrauzer, J. E. McGinness, and K. Knehn,Carcinogenesis 1, 199 (1980).
D. Medina and F. Shepherd,Cancer Lett. 8, 241 (1980).
G. A. Greeder and J. A. Milner,Science 209, 825 (1980).
C. Ip, M. Ip, and U. Kim,Cancer lett. 14, 101 (1981).
A. H. Daoud and A. C. Griffin,Cancer Lett. 5, 231 (1978).
W. V. Marshall, M. S. Arnott, M. M. Jacobs and A. C. Griffin,Cancer Lett. 7, 331 (1979).
A. C. Griffin,Adv. Cancer Res. 29, 419 (1979).
J. E. Spallhoz,Adv. Exp. Med. Biol. 135, 43 (1981).
M. M. Jacobs, T. S. Matney, and A. C. Griffin,Cancer Lett. 2, 319 (1977).
H. J. Thompson, and P. J. Becci,J. Natl. Cancer Inst. 65, 1299 (1980).
A. G. Gilman,Proc. Natl. Acad. Sci. USA 67, 305 (1970).
H. Boyd, D. A. McAfee, and J. Rubins,Tissue and Cell 10, 477 (1978).
W. J. Thompson, and M. M. Appleman,Biochemistry 10, 311 (1971).
R. Van Wijk, W. D. Wicks, M. M. Bevers, and J. Van Rijn,Cancer Res. 33, 1331 (1973).
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall,J. Biol. Chem. 193, 265 (1951).
D. L. Klayman, inOrganic Selenium Compounds: Their Chemistry and Biology, D. L. Klayman and W. H. Günther, eds., Wiley, New York, 1973, p. 727.
W. L. Ryan,Adv. Cyclic Nucleotide Res. 4, 81 (1979).
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An erratum to this article is available at http://dx.doi.org/10.1007/BF02988945.
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Yu, SY., Wang, LM. Different effects of selenium on cyclic AMP metabolism in hepatoma cells and normal liver cells. Biol Trace Elem Res 5, 9–16 (1983). https://doi.org/10.1007/BF02916922
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DOI: https://doi.org/10.1007/BF02916922