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
- 1 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
- 2 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
- 3 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
- 4 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
- 5 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
- 6 Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, China
Abstract
Aim: To study the antitumor mechanism of OSW-1 in hepatocellular carci noma. Materials and Methods: The expression profiling microarray was carried out to extract RNA from SK-Hep-1 which suffered from OSW-1 . ρ 0 -SK-Hep-1 was maintained SK-Hep-1 in MEM containing 100 μg/L ethi dium 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 record ed 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 nonma lignant cells are significantly less sensitive to OSW-1 than cancer cell lines.
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