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Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo.
Cancer Res. 2003 Sep 01; 63(17):5390-400.CR

Abstract

Tumor necrosis factor-related apoptosis-inducing-ligand (TRAIL/Apo-2 ligand) induces apoptosis in the majority of cancer cells without appreciable effect in normal cells. Here, we report the effects of TRAIL on apoptosis in several human breast cancer cell lines, primary memory epithelial cells, and immortalized nontransformed cell lines, and we examine whether chemotherapeutic agents augment TRAIL-induced cytotoxicity in breast cancer cells in vitro and in vivo. TRAIL induced apoptosis with different sensitivities, and the majority of cancer cell lines were resistant to TRAIL. The chemotherapeutic drugs (paclitaxel, vincristine, vinblastine, etoposide, camptothecin, and Adriamycin) induced death receptors (DRs) TRAIL receptor 1/DR4 and TRAIL receptor 2/DR5, and successive treatment with TRAIL resulted in apoptosis of both TRAIL-sensitive and -resistant cells. Actinomycin D sensitized TRAIL-resistant cells through up-regulation of caspases (caspase-3, -9, and -8). TRAIL induces apoptosis in Adriamycin-resistant MCF7 cells already expressing high levels of death receptors DR4 and DR5. The pretreatment of breast cancer cells with chemotherapeutic drugs followed by TRAIL reversed their resistance by triggering caspase-3, -9, and -8 activation. The sequential treatment of nude mice with chemotherapeutic drugs followed by TRAIL induced caspase-3 activity and apoptosis in xenografted tumors. Complete eradication of established tumors and survival of mice were achieved without detectable toxicity. Thus, the sequential administration of chemotherapeutic drugs followed by TRAIL may be used as a new therapeutic approach for cancer therapy.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Molecular and Cellular Biology Program, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201-1180, USA.No 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

14500373

Citation

Singh, Thiyam Ramsing, et al. "Synergistic Interactions of Chemotherapeutic Drugs and Tumor Necrosis Factor-related Apoptosis-inducing ligand/Apo-2 Ligand On Apoptosis and On Regression of Breast Carcinoma in Vivo." Cancer Research, vol. 63, no. 17, 2003, pp. 5390-400.
Singh TR, Shankar S, Chen X, et al. Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res. 2003;63(17):5390-400.
Singh, T. R., Shankar, S., Chen, X., Asim, M., & Srivastava, R. K. (2003). Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Research, 63(17), 5390-400.
Singh TR, et al. Synergistic Interactions of Chemotherapeutic Drugs and Tumor Necrosis Factor-related Apoptosis-inducing ligand/Apo-2 Ligand On Apoptosis and On Regression of Breast Carcinoma in Vivo. Cancer Res. 2003 Sep 1;63(17):5390-400. PubMed PMID: 14500373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. AU - Singh,Thiyam Ramsing, AU - Shankar,Sharmila, AU - Chen,Xufen, AU - Asim,Mohammed, AU - Srivastava,Rakesh K, PY - 2003/9/23/pubmed PY - 2003/11/7/medline PY - 2003/9/23/entrez SP - 5390 EP - 400 JF - Cancer research JO - Cancer Res VL - 63 IS - 17 N2 - Tumor necrosis factor-related apoptosis-inducing-ligand (TRAIL/Apo-2 ligand) induces apoptosis in the majority of cancer cells without appreciable effect in normal cells. Here, we report the effects of TRAIL on apoptosis in several human breast cancer cell lines, primary memory epithelial cells, and immortalized nontransformed cell lines, and we examine whether chemotherapeutic agents augment TRAIL-induced cytotoxicity in breast cancer cells in vitro and in vivo. TRAIL induced apoptosis with different sensitivities, and the majority of cancer cell lines were resistant to TRAIL. The chemotherapeutic drugs (paclitaxel, vincristine, vinblastine, etoposide, camptothecin, and Adriamycin) induced death receptors (DRs) TRAIL receptor 1/DR4 and TRAIL receptor 2/DR5, and successive treatment with TRAIL resulted in apoptosis of both TRAIL-sensitive and -resistant cells. Actinomycin D sensitized TRAIL-resistant cells through up-regulation of caspases (caspase-3, -9, and -8). TRAIL induces apoptosis in Adriamycin-resistant MCF7 cells already expressing high levels of death receptors DR4 and DR5. The pretreatment of breast cancer cells with chemotherapeutic drugs followed by TRAIL reversed their resistance by triggering caspase-3, -9, and -8 activation. The sequential treatment of nude mice with chemotherapeutic drugs followed by TRAIL induced caspase-3 activity and apoptosis in xenografted tumors. Complete eradication of established tumors and survival of mice were achieved without detectable toxicity. Thus, the sequential administration of chemotherapeutic drugs followed by TRAIL may be used as a new therapeutic approach for cancer therapy. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/14500373/Synergistic_interactions_of_chemotherapeutic_drugs_and_tumor_necrosis_factor_related_apoptosis_inducing_ligand/Apo_2_ligand_on_apoptosis_and_on_regression_of_breast_carcinoma_in_vivo_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=14500373 DB - PRIME DP - Unbound Medicine ER -