Sanguinarine,
chelerythrine and
chelidonine possess prominent apoptotic effects towards
cancer cells. In this study, we found that
sanguinarine and
chelerythrine induce apoptosis in human CEM T-
leukemia cells, and that is accompanied by an early increase in cytosolic
cytochrome c that precedes caspases-8, -9 and -3 processing. During apoptosis induction by
sanguinarine and
chelerythrine,
reactive oxygen species (ROS) was rapidly generated and DeltaPsi(mt) dissipated, while Bax, Bcl-2 and Bcl-X((L/S))
proteins' content in the mitochondrial fraction did not change significantly.
Caspase-3 activation and DNA fragmentation were considerably inhibited by N-acetyl-
cysteine (NAC).
Chelidonine induced only a slight release of
cytochrome c (12h), parallel to
caspase-3 activation. Effect of
sanguinarine or
chelerythrine towards mitochondria was confirmed by marked changes in morphology of this organelle (3h), while
chelidonine did not affect mitochondria intactness.
Sanguinarine or
chelerythrine also caused an intensive DNA damage in cells in 1h, however a massive increase in number of such impaired cells occurred in 6h, while
chelidonine induced intensive DNA damage in 15-20% cells only in 24h. Thus, our results demonstrated that rapid
cytochrome c release in CEM T-
leukemia cells exposed to
sanguinarine or
chelerythrine was not accompanied by changes in Bax, Bcl-2 and Bcl-X((L/S))
proteins in the mitochondrial fraction, and preceded activation of the initiator
caspase-8.