Loss of pigment in hamster
amelanotic melanoma line is accompanied by a faster growth rate, higher tumorigenicity and shorter animal survival time. Thus, the
malignancy of
melanoma increases during the alteration of melanotic (Ma) into amelanotic (Ab) line. As changes in the ability to undergo a spontaneous or induced apoptosis, and the role of
caspases in this process during
melanoma progression are not well defined, they were investigated in this work. Our results show that the proportion of spontaneously early apoptotic (
caspase+/PI-) cells in the Ab line decreased in comparison to the Ma line.
Cytochrome c release into cytosol, and the activation of
effector caspases, estimated by PARP degradation clearly showed that during the spontaneous death in the cells from both
melanoma lines intrinsic way of apoptosis was activated. Confocal and cytometric flow analyses indicate that
camptothecin (
CPT) induced apoptosis with
caspase activation by the intrinsic way only in the
amelanotic melanoma cells, even though cells of the Ma line also underwent
CPT-induced apoptosis (the content of TUNEL-positive cells increased). Thus, our results suggest that
melanoma progression, associated with a decreased ability to undergo spontaneous apoptosis but an increased susceptibility to
CPT-induced apoptosis, relates to different levels of
caspase activation; they also show that intrinsic way of apoptotis depends on the phenotype of
melanoma cells, being more pronounced in the melanotic
melanoma cells. On the other hand, melanotic
melanoma cells resistance to
camptothecin-induced apoptosis suggests that the melanogenic apparatus or
melanin itself may have the protective effect on the ability of the
melanoma cells to undergo apoptosis.