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Experimental Therapeutics, Preclinical Pharmacology |
Departments of Radiation Oncology [G. G. H., J. D. F., M. Y., R. L. M., J. R., A. L., S. T-M.], Internal Medicine [O. K.], Integrated Biostatistics Unit [S. T-M., J. A.], and Pathology [F. H. S.], Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, and Harper Hospital, Detroit, Michigan 48201
We have shown previously that genistein, the major isoflavone in
soybean, inhibited the growth of human prostate cancer cells in
vitro by affecting the cell cycle and inducing apoptosis. To
augment the effect of radiation for prostate carcinoma, we have now
tested the combination of genistein with photon and neutron radiation
on prostate carcinoma cells in vitro. The effects of
photon or neutron radiation alone or genistein alone or both combined
were evaluated on DNA synthesis, cell growth, and cell ability to form
colonies. We found that neutrons were more effective than photons for
the killing of prostate carcinoma cells in vitro,
resulting in a relative biological effectiveness of 2.6 when compared
with photons. Genistein at 15 µM caused a significant
inhibition in DNA synthesis, cell growth, and colony formation in the
range of 4060% and potentiated the effect of low doses of 200300
cGy photon or 100150 cGy neutron radiation. The effect of the
combined treatment was more pronounced than with genistein or radiation
alone. Our data indicate that genistein combined with radiation
inhibits DNA synthesis, resulting in inhibition of cell division and
growth. Genistein can augment the effect of neutrons at doses
2-fold
lower than photon doses required to observe the same efficacy. These
studies suggest a potential of combining genistein with radiation for
the treatment of localized prostate carcinoma.
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