Potentiation of the radiation effect with genistein in cervical cancer cells.
OBJECTIVE
Early stage cervical cancer is treated with surgery or radiation with equivalent results. Radiation is used for curative therapy of locally advanced disease and is combined with additional anti-tumor agents to improve control. We determined the potential role of genistein as a radiosensitizer for cervical cancer cells.


METHODS
Human cervical cell lines (CaSki and ME180) were used. Sensitivity of cells to genistein, radiation and the combination was determined by colony assays. Western blotting was used to study the expression of cell-response-related gene products.


RESULTS
Genistein results in the dose-dependent inhibition of all cell lines (2.5-40.0 microM). Effect of genistein on the radiosensitivity of the two cervical tumor cells was variable. Me180 cells were more sensitive at 20 and 40 microM of genistein. At 40 microM, less than 5% of Me180 cells survived the radiation (200-800 cGy). Potentiation of the radiation effect in CaSki cells was seen (500-800 cGy). The most significant enhancement of radiosensitivity was seen at 20 and 40 microM genistein at 500 and 800 cGy. G(2)M arrest was demonstrated only in ME180 cells with genistein. There was significant inhibition of Mcl-1 by genistein that correlated with increase in radiosensitivity in Me180 cells. Activated pAKT (Thr 308) was inhibited with genistein and radiation in CaSki cells. CONCLUSIONS.: Genistein inhibits growth of cervical cancer cells. Genistein results in variable and significant enhancement of the radiation effect that may be partially mediated by G(2)M arrest, Mcl-1 and activation of the AKT gene.
Yashar
Catheryn M
CM
Department of Radiation Oncology, University of Louisville School of Medicine, 511 South Floyd Street, Room 416, Louisville, KY 40202, USA.
Spanos
William J
WJ
Taylor
Douglas D
DD
Gercel-Taylor
Cicek
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D045304:Cytochromes c / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000009:adverse effects / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D007529:Isoflavones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; C004742:daidzein; D045304:Cytochromes c; D019833:Genistein; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt