The present studies were aimed at testing the hypothesis that
nitric oxide (NO) may enhance
Taxol-induced cytotoxicity in
carcinoma cells by increasing influx of
Taxol into intracellular compartments. Prostate
carcinoma cells (PC-3, LNCaP) and
neuroblastoma cells (SKNDZ, CHP212) were used to investigate both transmembrane permeability and cytotoxicity of
Taxol in the presence and absence of
S-nitrosocaptopril (CapNO), a
nitric oxide donating compound. The order of permeability rate of
Taxol across the four cell lines was SKNDZ>LNCaP>PC-3>CHP212. Pretreatment of the cell lines with CapNO (100 microM) enhanced permeability of
Taxol across prostate PC-3 and LNCaP cells, but not
neuroblastoma SKNDZ and CHP212 cells.
Taxol inhibited cell growth at nanomolar levels with IC(50)s of 0.21, 17.4, 96.4 and 842.9 nM corresponding to SKNDZ, PC-3, LNCaP and CHP212 cells, respectively. However, CapNO inhibited proliferation of the four cell lines at millimolar levels with IC(50)s ranging from 0.3 to 1.1 mM. Enhancing effect of CapNO (100 microM) on
Taxol cytotoxicity were found in PC-3 and LNCaP cells, but not in SKNDZ and CHP212. The findings suggest that the cytotoxic potency of
Taxol is mainly dependent upon the cell membrane permeabilization to
Taxol, and the enhancing effect of CapNO on
Taxol-induced cytotoxicity is primarily mediated via the increased influx of
Taxol by NO into intracellular compartments, while NO-induced cytotoxicity cannot be excluded.