Genistein potentiates the radiation effect on prostate carcinoma cells.
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 microM caused a significant inhibition in DNA synthesis, cell growth, and colony formation in the range of 40-60% and potentiated the effect of low doses of 200-300 cGy photon or 100-150 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 approximately 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.
Hillman
G G
GG
Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, and Harper Hospital, Detroit, Michigan 48201, USA. hillmang@karmanos.org
Forman
J D
JD
Kucuk
O
O
Yudelev
M
M
Maughan
R L
RL
Rubio
J
J
Layer
A
A
Tekyi-Mensah
S
S
Abrams
J
J
Sarkar
F H
FH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000528:radiation effects*; D005720:Gamma Rays; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013936:Thymidine / Q000737:chemistry; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D004247:DNA; D019833:Genistein; D013936:Thymidine