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J Korean Soc Ther Radiol Oncol > Volume 20(4); 2002 > Article
The Journal of the Korean Society for Therapeutic Radiology and Oncology 2002;20(4): 367-374.
A Novel Chenodeoxycholic Derivative HS-1200 Induces Apoptosis in Human HT-29 Colon Cancer Cells
Sin Geun Oh, Kwang Mo Yang, Won Joo Hur, Young Hyun Yoo, Hong Suk Suh, Hyung Sik Lee
1Department of Radiation Oncology, College of Medicine, Dong A University, Korea. hyslee@daunet.donga.ac.kr
2Department of Anatomy, College of Medicine, Dong A University, Korea.
3Department of Cell Biology, College of Medicine, Dong A University, Korea.
4Department of Chemistry, Pusan National University, Busan, Korea.
To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile acid derivative (HS-1200).
Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-29 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses.
The dose required for the half maximal inhibition (IC50) of the HT-29 cell growth was 100~150 micro M of HS-1200. Several changes, associated with the apoptosis of the HT-29 cells, were reveal by the agarose gel eletrophoresis, TUNEL assays and Hoechst staining, following their treatment with 100 micro M of HS-1200. HS-1200 treatment also induced caspase-3, PARP and DFF degradations, and the western blotting showed the processed caspase-3 p20, PARP p85 and DFF p30 and p11 cleaved products. Mitochondrial events were also demonstrated. The cytochrome c staining indicated that cytochrome c had been released from the mitochondria in the HS-1200 treated cells. The mitochondrial membrane potential (deltaxm) was also prominently decreased in the HS-1200 treated cells.
These findings suggest that the HS-1200 - induced apoptosis of human colon cancer cells (HT-29) is mediated via caspase and mitochondrial pathways.
Key Words: Bile acids, CDCA derivatives-induced apoptosis, Mitochondrial pathway
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