[Enhancing effect of isoflavonoid genistein on radiosensitivity of DU145 prostate cancer cells].
To study the enhancing effect of isoflavonoid genistein in irradiation (IR) on prostate DU145 cancer cells.



Prostate cancer cell line DU145 was used in this experiment. Clonogenic assay was applied to compare the survival fractions of DU145 cells after treatments with genistein alone and/or graded IR. DNA electrophoresis and TUNEL method were applied to detect cell apoptosis. Cell cycle was observed using flow cytometry and related protein expressions by immunoblotting.



Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. After treatments with IR and/or genistein for 24 h, apoptosis was mainly seen with genistein at high concentration and was minimally dependent on IR. Apoptosis also occurred after treatments for 72 h with lower concentrations of genistein, especially when combined with IR. While IR or genistein led to a G2/M cell cycle arrest, combination of them could further increase DU145 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, and accompanied by increasing apoptosis and hyperdiploid cell populations. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1, less markedly increased cdc-2 and stably elevated p21(cip1) levels with increasing genistein concentrations.



Genistein could enhance the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair induced by the combined treatment.
Yan
Sen-xiang
SX
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Zheng
Shu-sen
SS
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016203:CDC2 Protein Kinase / Q000032:analysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019926:Cyclin B / Q000032:analysis; D056744:Cyclin B1; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D011838:Radiation-Sensitizing Agents; D019833:Genistein; D016203:CDC2 Protein Kinase