Estramustine: a novel radiation enhancer in human carcinoma cells.
OBJECTIVE
Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G2/M phase of the cell cycle. Since cells in the G2/M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells.


METHODS
Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S3) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves.


RESULTS
Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 microM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G2/M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations.


CONCLUSIONS
The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity.
Ryu
S
S
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202.
Gabel
M
M
Khil
M S
MS
Lee
Y J
YJ
Kim
S H
SH
Kim
J H
JH
D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D003131:Combined Modality Therapy; D004961:Estramustine / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014747:Vinblastine / Q000494:pharmacology
D011838:Radiation-Sensitizing Agents; D004961:Estramustine; D014747:Vinblastine; D017239:Paclitaxel