R. Ikeda et al., Induction of apoptosis in mice with B16 melanoma by treatment with the antimicrotubule agent TZT-1027, ACT HIST CY, 33(5), 2000, pp. 341-347
TZT-1027, an inhibitor of tubulin polymerization, is a derivative of dolast
atin 10 isolated from the Indian Ocean sea hare Dolabella auricularia. TZT-
1027 has good anticancer activity.
We investigated the effect on B16 melanoma of TZT-1027 in mice histopatholo
gically and by agarose gel electrophoresis. At 1 mg/kg of TZT-1027, there w
as a good correlation between the number of mitosis-like cells and apoptoti
c bodies. In mitosis-like cells, the nuclear membrane had disappeared, and
the chromosomes had morphological features typical of mitosis. However, not
all cells in mitosis had proliferated. In contrast, at 2 mg/kg of TZT-1027
, many apoptotic bodies were detected soon after treatment, but these were
not involved in the dynamic changes to mitosis-like cells. Furthermore, TUN
EL-positive cells were clearly visible at 1 hr after treatment and the nucl
ei of these cells showed chromatin margination, cap-shape chromatin clampin
g, and nuclear condensation on electron microscopy.
Therefore, we speculated that the effect on B16 melanoma cells of TZT-1027
differed with the treatment dose, and a dose of 2 mg/kg induces apoptosis i
n tumor cells by a direct mechanism.