Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines.
Paclitaxel is a deterpene with antitumor activity against a variety of human neoplasms. Paclitaxel cytotoxicity is thought to derive mainly from a stabilization of microtubules as a result of enhanced tubulin polymerization that leads to an accumulation of cells in the mitotic (M) phase of the cell cycle. Because cells in this phase of the cell cycle are known to be radiosensitive, it was thought that paclitaxel, in addition to its direct toxicity, may also sensitize tumor cell populations to radiation. Studies evaluating the radiosensitizing potential of paclitaxel in cultured cells have been equivocal, with only approximately 50% of the tested cell lines showing radiosensitization. To explain this variability, we advanced the hypothesis that the ability of paclitaxel to radiosensitize cells may be inversely correlated to the efficiency with which it induces apoptosis. To test this hypothesis, we studied paclitaxel-induced apoptosis and radiosensitization in seven human tumor cell lines. Approximately one-half of these cell lines showed radiosensitization that was associated with a low apoptotic index (<20% after a 48-h treatment with 10 or 20 nM paclitaxel). The results suggest that the level of apoptosis, after paclitaxel treatment, may predict for paclitaxel-induced radiosensitization, and that it could be introduced as a parameter for the optimization of combined treatment protocols.
Kurdoglu
B
B
Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Cheong
N
N
Guan
J
J
Corn
B W
BW
Curran
W J
WJ
Iliakis
G
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D017239:Paclitaxel / Q000494:pharmacology*; D011237:Predictive Value of Tests; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D006131:Growth Inhibitors; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel