Trichosanthin induced calcium-dependent generation of reactive oxygen species in human choriocarcinoma cells
2000
The type-I ribosome-inactivating protein trichosanthin (TCS)
has a broad spectrum of biological and pharmacological activities,
including abortifacient, anti-tumor and anti-HIV. We found for the first
time that TCS induced the generation of reactive oxygen species (ROS) in
human choriocarcinoma cells (JAR cells) at the level of the single cell by
using the fluorescent probe 2′,7′-dichlorofluorescein diacetate
with confocal laser scanning microscopy. TCS-induced ROS formation was
shown to be dependent on the presence of extracellular Ca2+ and
was further reduced when cytosolic Ca2+ was chelated by
BAPTA-AM. The production of ROS increased rapidly after the application of
TCS, which paralleled TCS-induced increase in intracellular calcium
monitored using fluo 3-AM. Simultaneous observation of the nuclear
morphological changes via two-photon laser scanning microscopy and
production of ROS via confocal laser scanning microscopy revealed
that ROS were involved in the apoptosis of JAR cells. The contribution of
ROS was confirmed by experiments in which the antioxidant
α-tocopherol prevented TCS-induced ROS formation and cell death. The
finding that TCS induced calcium-dependent generation of ROS in JAR cells
and that ROS were involved in the apoptosis of JAR cells might provide new
insight into the anti-tumor and anti-HIV mechanism of TCS.
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