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Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis.
Cancer Res. 2001 Feb 15; 61(4):1645-51.CR

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new cytokine that was proposed to specifically induce apoptosis of cancer cells. In tumor cells that are resistant to the cytokine, subtoxic concentrations of chemotherapeutic drugs can restore the response to TRAIL. The present study further explores the mechanisms that determine tumor cell sensitivity to TRAIL by comparing four human colon carcinoma cell lines We show that colon cancer cell sensitivity to TRAIL-induced apoptosis and cytotoxicity correlates with the expression of the death receptors TRAIL-R1 and TRAIL-R2 at the cell surface, as determined by now cytometry, whereas the two decoy receptors TRAIL-R3 and TRAIL-R4 can be detected only in permeabilized cells. Clinically relevant concentrations of cisplatin and doxorubicin sensitize the most resistant colon cancer cell lines to TRAIL-induced cell death without modifying the expression nor the localization of TRAIL receptors in these cells. TRAIL induces the activation of procaspase-8 and triggers caspase-dependent apoptosis off colon cancer cells. Cytotoxic drugs lower the signaling threshold required for TRAIL-induced procaspase-8 activation. In turn, caspase-8 cleaves Bid, a BH3 domain-containing proapoptotic molecule of the Bcl-2 family and activates effector caspases. Together, these data indicate that chemotherapeutic drugs sensitize colon tumor cells to TRAIL-mediated caspase-8 activation and apoptosis.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale U517, Facultés de Médicine et de Pharmacie, Dijon, France.No affiliation info availableNo 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

11245478

Citation

Lacour, S, et al. "Anticancer Agents Sensitize Tumor Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated Caspase-8 Activation and Apoptosis." Cancer Research, vol. 61, no. 4, 2001, pp. 1645-51.
Lacour S, Hammann A, Wotawa A, et al. Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. Cancer Res. 2001;61(4):1645-51.
Lacour, S., Hammann, A., Wotawa, A., Corcos, L., Solary, E., & Dimanche-Boitrel, M. T. (2001). Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. Cancer Research, 61(4), 1645-51.
Lacour S, et al. Anticancer Agents Sensitize Tumor Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated Caspase-8 Activation and Apoptosis. Cancer Res. 2001 Feb 15;61(4):1645-51. PubMed PMID: 11245478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. AU - Lacour,S, AU - Hammann,A, AU - Wotawa,A, AU - Corcos,L, AU - Solary,E, AU - Dimanche-Boitrel,M T, PY - 2001/3/14/pubmed PY - 2001/4/3/medline PY - 2001/3/14/entrez SP - 1645 EP - 51 JF - Cancer research JO - Cancer Res VL - 61 IS - 4 N2 - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new cytokine that was proposed to specifically induce apoptosis of cancer cells. In tumor cells that are resistant to the cytokine, subtoxic concentrations of chemotherapeutic drugs can restore the response to TRAIL. The present study further explores the mechanisms that determine tumor cell sensitivity to TRAIL by comparing four human colon carcinoma cell lines We show that colon cancer cell sensitivity to TRAIL-induced apoptosis and cytotoxicity correlates with the expression of the death receptors TRAIL-R1 and TRAIL-R2 at the cell surface, as determined by now cytometry, whereas the two decoy receptors TRAIL-R3 and TRAIL-R4 can be detected only in permeabilized cells. Clinically relevant concentrations of cisplatin and doxorubicin sensitize the most resistant colon cancer cell lines to TRAIL-induced cell death without modifying the expression nor the localization of TRAIL receptors in these cells. TRAIL induces the activation of procaspase-8 and triggers caspase-dependent apoptosis off colon cancer cells. Cytotoxic drugs lower the signaling threshold required for TRAIL-induced procaspase-8 activation. In turn, caspase-8 cleaves Bid, a BH3 domain-containing proapoptotic molecule of the Bcl-2 family and activates effector caspases. Together, these data indicate that chemotherapeutic drugs sensitize colon tumor cells to TRAIL-mediated caspase-8 activation and apoptosis. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11245478/Anticancer_agents_sensitize_tumor_cells_to_tumor_necrosis_factor_related_apoptosis_inducing_ligand_mediated_caspase_8_activation_and_apoptosis_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11245478 DB - PRIME DP - Unbound Medicine ER -