Apoptosis as a predictor of paclitaxel-induced radiosensitization in humantumor cell lines

Paclitaxel is a deterpene with antitumor activity against a variety of huma n neoplasms. Paclitaxel cytotoxicity is thought to derive; mainly from a st abilization of microtubules asa result of enhanced tubulin polymerization t hat 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 radios ensitive, it was thought that paclitaxel, in addition to its direct toxicit y, may also sensitize tumor cell populations to radiation. Studies evaluati ng the radiosensitizing potential of paclitaxel in cultured cells have been equivocal, with only similar to 50% of the tested cell lines showing radio sensitization, To explain this variability, we advanced the hypothesis that the ability of paclitaxel to radiosensitize cells may be inversely correla ted to the efficiency with which it induces apoptosis, To test this hypothe sis, we studied paclitaxel-induced apoptosis and radiosensitization in seve n human tumor cell lines. Approximately one-half of these cell lines showed radiosensitization that was associated with a low apoptotic index (<20% af ter a 48-h treatment with 10 or 20 nM paclitaxel), The results suggest that the level of apoptosis, after paclitaxel treatment, may predict for paclit axel-induced radiosensitization, and that it could be introduced as a param eter for the optimization of combined treatment protocols.