Table 3.

Cytotoxicity profile of MAC-321 versus standard chemotherapeutics in PTX- and Epo-resistant cell lines that contain mutations in the taxane-binding site of β-tubulina

CompoundIC50 (nm)*
Relative Resistanceb
1A91A9 PTX101A9 PTX221A9 EpoA81A9 PTX101A9 PTX22EpoA8
MAC -3211.6 ± 0.65.4 ± 2.78 ± 1.42.6 ± 1.63.45.01.6
PTX5.1 ± 1.026.6 ± 16.389.2 ± 55.620.9 ± 10.85.217.54.1
DTX1.8 ± 0.67.5 ± 0.37.9 ± 0.22.2 ± 1.24.24.41.2
EpoA1.8 ± 0.516.0 ± 49.04.1 ± 3.331.8 ± 14.08.92.317.7
Compound
IC50 (nm)**
Relative Resistanceb
A549
A549.EpoB40
A549.EpoB40
MAC-3211.1 ± 0.611.3 ± 1.210.7
PTX7.5 ± 1.3156.9 ± 16.920.8
DTX1.9 ± 0.731.8 ± 1.616.6
EpoB1.0 ± 0.191.5 ± 3.995.3
  • a Parental cells and their resistant cell counterpart were grown in the presence of the indicated agents for 3 days and growth assessed by SRB staining (*) or ATP-binding (**) as described in “Materials and Methods.” Data are reported as average IC50 ± SD.

  • b Average relative resistance is defined as the ratio of the IC50 of the resistant cell model to that of the respective sensitive/parental cell counterpart.