Publication: Binding of tumour necrosis factor-alpha (TNF-α) to TNF-RI induces caspase(s)-dependent apoptosis in human cholangiocarcinoma cell lines
Issued Date
1999-04-20
Resource Type
ISSN
00099104
Other identifier(s)
2-s2.0-0032902154
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical and Experimental Immunology. Vol.116, No.1 (1999), 41-47
Suggested Citation
P. Utaisincharoen, S. Ubol, N. Tangthawornchaikul, P. Chaisuriya, S. Sirisinha Binding of tumour necrosis factor-alpha (TNF-α) to TNF-RI induces caspase(s)-dependent apoptosis in human cholangiocarcinoma cell lines. Clinical and Experimental Immunology. Vol.116, No.1 (1999), 41-47. doi:10.1046/j.1365-2249.1999.00856.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/25445
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Binding of tumour necrosis factor-alpha (TNF-α) to TNF-RI induces caspase(s)-dependent apoptosis in human cholangiocarcinoma cell lines
Other Contributor(s)
Abstract
Cholangiocarcinoma (CCA), a tumour of the bite duct epithelium, occurs with a higher incidence in South-east Asian countries than in Europe and North America. The prognosis is poor, due to the unavailability of early diagnosis and the tumours being relatively resistant to chemotherapy. In the present study one of the fatal routes of this tumour was studied. This death was stimulated by TNF-α. TNF-α at a concentration of 760 pg/ml and 100 pg/ml in the presence of 1 μg/ml actinomycin D induced 50% cell death of the two established human cholangiocarcinoma cell lines HuCCA-1 and HuCCA-1Nu, respectively. Preincubation of both cell lines with MoAb to TNF-RI or TNF- RII before TNF-α treatment showed that only the MoAb specific to TNF-RI inhibited death. The death of these two cell lines was proved to be apoptosis. Western blot analysis of extracts from both cell lines demonstrated a cleavage of poly (ADP-ribose) polymerase (PARP) within 6-8h following TNF-α treatment. The degradation of PARP was prevented by a MoAb to TNF-RI indicating that the TNF-RI but not TNF-RII was involved in TNF- induced apoptosis in these two human cholangiocarcinoma cell lines. Moreover, peptide inhibitor for caspase II subfamily, Ac-DEVD-CHO, reduced the cytolysis of TNF-α-treated cholangiocarcinoma cells. The inhibitor also prevented degradation of PARP. These results indicate that the interaction between TNF-α and TNF-RI alone generated a sufficient signal to activate a caspase II subfamily-dependent apoptosis in human cholangiocarcinoma cell lines.