OSW-1 Induced Apoptosis in Hepatocellular Carcinoma through Generation of ROS, Cytochrome C and Noxa Activation Independent of p53 with Non-Activation of Caspase-3
Aim: To study the antitumor mechanism of OSW-1 in hepatocellular
carcinoma. Materials and Methods: The expression profiling microarray wascarried
out to extract RNA from SK-Hep-1 which suffered from OSW-1.ρ0-SK-Hep-1 was maintained SK-Hep-1 in MEM
containing 100 μg/L ethidium bromide (EB), 1 mM sodium pyruvate and 50
μg/ml uridine for 40 days. Then confirmed
COX-I and COX-II of mitochondrial DNA were knocked out. Cells suffered
from OSW-1 or doxorubicin. Then cells were washed twice with cold PBS and incubated with DCFH-DA. Fluorescent signal was recorded by using Infinite 200 Pro multimode Plate
readers. Results: OSW-1 elevates generation of ROS and Cytochrome C
which are associated with the induction of apoptosis in SK-Hep-1 cells. We also
demonstrate that OSW-1 does not depend on p53
to up-regulate the BH3-only protein Noxa. What is more noteworthy that
the Caspase-9 and FADD are down-regulated in above process. Conclusion: OSW-1 induced special apoptosis is different from
the mitochondrial death pathway and the death receptor pathway and final
result is not Caspase family’s activating.
This provides a novel theory that nonmalignant cells are significantly
less sensitive to OSW-1 than cancer cell lines.
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