Taxol is an antitumor drug with cytotoxic properties that correlate with its microtubule-stabilizing activities. It has been reported that taxol parallels lipopolysaccharide in its effects on the induction of tumor necrosis factor-α (TNF-α) gene expression in macrophages (C. Bogdan and A. Ding, J. Leukocyte Biol., 52: 119–121, 1992; C. L. Manthey, M. E. Brandes, P. Y. Perera, and S. Vogel, J. Immunol., 149: 2459–2465, 1992; J. M. Carboni, C. Singh, and M. A. Tepper, Natl. Cancer Inst. Monogr., 15: 95–101, 1993). Structure-activity studies using taxol and related taxanes have been done to determine the relationship between the effects of taxol on TNF-α gene expression and its cytotoxic and microtubule-stabilizing activities. Using Northern blot analysis, it was found that changes in the structure of taxol that did not alter cytotoxicity did prevent the induction of TNF-α gene expression. The data presented in this paper demonstrate that the effects of taxol on TNF-α gene expression are distinct from its known cytotoxic properties.
This study was supported by USPHS Grants CA 39821 (S. B. H.), N511920, (J. W. B.), and CA 55139 (C. S. S.).