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Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis.
Anticancer Res. 2006 Jan-Feb; 26(1A):259-65.AR

Abstract

BACKGROUND

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) promotes apoptosis by binding to transmembrane receptors. It is known to induce apoptosis in a wide variety of cancer cells, but TRAIL-resistant cancers have also been documented. In this study, the relative resistance of human cholangiocarcinoma (CCA) cell lines against TRAIL-induced apoptosis is reported and the possible potential synergistic effect with triptolide, a diterpene triepoxide extracted from the Chinese herb Tripterygium wilfordii, in killing TRAIL-resistant CCA cells is investigated.

MATERIALS AND METHODS

Six human CCA cell lines were treated with various concentrations of TRAIL and the resistant cells were identified and subsequently tested for their sensitivity to a combination of TRAIL and triptolide. The susceptibility and resistance of the cells were based on analysis of cytotoxic and apoptotic induction and expression of anti-apoptotic factors (Mcl-1 and cFLIP).

RESULTS

The treatment of TRAIL induced a dose-dependent decrease in cell viability in 4 out of the 6 cell lines. A combination of TRAIL and triptolide enhanced cytotoxicity and apoptosis in these 2 resistant cell lines. The combined treatment enhanced activation of caspase-8 and its downstream signaling processes compared with the treatment with either one alone.

CONCLUSION

The results presented show that human CCA cells were heterogeneous with respect to susceptibility to TRAIL-induced apoptosis. The combination of TRAIL and triptolide could enhance susceptibility to TRAIL-induced apoptotic killing in these TRAIL-resistant CCA cells, thus offering an alternative approach for the treatment of TRAIL-resistant cholangiocarcinoma.

Authors+Show Affiliations

Laboratory of Immunology, Chulabhom Research Institute, Bangkok, Thailand. tasanee_p@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16475706

Citation

Panichakul, Tasanee, et al. "Triptolide Sensitizes Resistant Cholangiocarcinoma Cells to TRAIL-induced Apoptosis." Anticancer Research, vol. 26, no. 1A, 2006, pp. 259-65.
Panichakul T, Intachote P, Wongkajorsilp A, et al. Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis. Anticancer Res. 2006;26(1A):259-65.
Panichakul, T., Intachote, P., Wongkajorsilp, A., Sripa, B., & Sirisinha, S. (2006). Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis. Anticancer Research, 26(1A), 259-65.
Panichakul T, et al. Triptolide Sensitizes Resistant Cholangiocarcinoma Cells to TRAIL-induced Apoptosis. Anticancer Res. 2006 Jan-Feb;26(1A):259-65. PubMed PMID: 16475706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis. AU - Panichakul,Tasanee, AU - Intachote,Pakamas, AU - Wongkajorsilp,Adisak, AU - Sripa,Banchob, AU - Sirisinha,Stitaya, PY - 2006/2/16/pubmed PY - 2006/3/10/medline PY - 2006/2/16/entrez SP - 259 EP - 65 JF - Anticancer research JO - Anticancer Res VL - 26 IS - 1A N2 - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) promotes apoptosis by binding to transmembrane receptors. It is known to induce apoptosis in a wide variety of cancer cells, but TRAIL-resistant cancers have also been documented. In this study, the relative resistance of human cholangiocarcinoma (CCA) cell lines against TRAIL-induced apoptosis is reported and the possible potential synergistic effect with triptolide, a diterpene triepoxide extracted from the Chinese herb Tripterygium wilfordii, in killing TRAIL-resistant CCA cells is investigated. MATERIALS AND METHODS: Six human CCA cell lines were treated with various concentrations of TRAIL and the resistant cells were identified and subsequently tested for their sensitivity to a combination of TRAIL and triptolide. The susceptibility and resistance of the cells were based on analysis of cytotoxic and apoptotic induction and expression of anti-apoptotic factors (Mcl-1 and cFLIP). RESULTS: The treatment of TRAIL induced a dose-dependent decrease in cell viability in 4 out of the 6 cell lines. A combination of TRAIL and triptolide enhanced cytotoxicity and apoptosis in these 2 resistant cell lines. The combined treatment enhanced activation of caspase-8 and its downstream signaling processes compared with the treatment with either one alone. CONCLUSION: The results presented show that human CCA cells were heterogeneous with respect to susceptibility to TRAIL-induced apoptosis. The combination of TRAIL and triptolide could enhance susceptibility to TRAIL-induced apoptotic killing in these TRAIL-resistant CCA cells, thus offering an alternative approach for the treatment of TRAIL-resistant cholangiocarcinoma. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/16475706/Triptolide_sensitizes_resistant_cholangiocarcinoma_cells_to_TRAIL_induced_apoptosis_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=16475706 DB - PRIME DP - Unbound Medicine ER -