Targeting Apoptosis by Hydroxymethylacylfulvene in Combination with Gamma Radiation in Prostate Tumor Cells
| Autor: | John R. MacDonald, Jan M. Woynarowski, Barbara A. Woynarowska, Kari Roberts, Terence S. Herman |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Radiation-Sensitizing Agents Pathology medicine.medical_specialty Neoplasms Hormone-Dependent medicine.medical_treatment Biophysics Apoptosis Adenocarcinoma Cell morphology Radiation Tolerance Flow cytometry Prostate cancer Tumor Cells Cultured medicine Humans Radiology Nuclear Medicine and imaging Intestinal Mucosa Clonogenic assay Antineoplastic Agents Alkylating Tumor Stem Cell Assay Radiation medicine.diagnostic_test business.industry Prostatic Neoplasms medicine.disease Combined Modality Therapy Radiation therapy Terminal deoxynucleotidyl transferase Gamma Rays Androgens Cancer research business Sesquiterpenes DNA Damage |
| Zdroj: | Radiation Research. 154:429-438 |
| ISSN: | 1938-5404 0033-7587 |
| Popis: | Hydroxymethylacylfulvene (HMAF) is a novel agent with alkylating activity and is a potent inducer of apoptosis that is currently undergoing Phase II clinical trials for prostate cancer. This study explored the pro-apoptosis and anti-proliferative potential of HMAF in combination with gamma radiation in human prostate tumor cell lines. Apoptosis was assessed based on the generation of fragmented DNA, a terminal transferase flow cytometry assay, and cell morphology. In each of the tumor cell lines examined, radiation alone induced a marginal level of apoptosis, even after a prolonged 48-h incubation after exposure. In contrast, HMAF alone was a potent inducer of apoptosis in prostate tumor cells but not in normal cells. Marked levels of apoptosis in tumor cells were also observed for the combination of HMAF with gamma radiation. When drug treatment preceded irradiation, at least additive levels of apoptosis were observed in both androgen-responsive and androgen-independent cells. The combined treatment with ionizing radiation and HMAF reduced the radiation dose needed for the same level of clonogenic survival up to 2.5-fold. The potentiation of apoptosis and reduction in the clonogenic survival of tumor cells occurred at HMAF concentrations lower than that which reduced survival to 10% and at doses up to 6 Gy. No potentiation of apoptosis or clonogenic inhibition was noted in normal cells. These results suggest that the combination of HMAF with gamma radiation may have clinical utility for treatments of prostate cancer. |
| Databáze: | OpenAIRE |
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