Tags

Type your tag names separated by a space and hit enter

Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential.
J Orthop Res. 2003 Sep; 21(5):949-57.JO

Abstract

Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. In the present study, we examined whether chemotherapeutic agents enhance TRAIL-induced apoptosis in the sarcoma cell lines MG-63 and SaOS-2. Pretreatment with sub-toxic or slightly toxic concentrations of chemotherapeutic agents (cis-diammine dichloroplatinum, CDDP and doxorubicin, DXR) sensitized both cell lines to TRAIL-induced apoptosis, as assessed by the propidium iodide or Annexin V-Cy5 staining method. These cell lines expressed death receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry. The decoy receptors TRAIL-R3 and -R4 were barely detected in both cell lines. CDDP down-regulated c-FLIP, tending to lower the activation threshold required for TRAIL-induced caspase-8 activation. The CDDP-pretreated cells indeed demonstrated more increased TRAIL-mediated caspase-8 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and apoptosis than untreated cells. Consequently, the activated caspase-8 might lead to either activation of effector caspases such as caspase-3 or loss in DeltaPsi(m). Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS.

Authors+Show Affiliations

Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12919886

Citation

Hotta, Takahito, et al. "Chemotherapeutic Agents Sensitize Sarcoma Cell Lines to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Caspase-8 Activation, Apoptosis and Loss of Mitochondrial Membrane Potential." Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, vol. 21, no. 5, 2003, pp. 949-57.
Hotta T, Suzuki H, Nagai S, et al. Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. J Orthop Res. 2003;21(5):949-57.
Hotta, T., Suzuki, H., Nagai, S., Yamamoto, K., Imakiire, A., Takada, E., Itoh, M., & Mizuguchi, J. (2003). Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 21(5), 949-57.
Hotta T, et al. Chemotherapeutic Agents Sensitize Sarcoma Cell Lines to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Caspase-8 Activation, Apoptosis and Loss of Mitochondrial Membrane Potential. J Orthop Res. 2003;21(5):949-57. PubMed PMID: 12919886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. AU - Hotta,Takahito, AU - Suzuki,Hidekazu, AU - Nagai,Shuzou, AU - Yamamoto,Kengo, AU - Imakiire,Atsuhiro, AU - Takada,Eiko, AU - Itoh,Mizue, AU - Mizuguchi,Junichiro, PY - 2003/8/16/pubmed PY - 2003/9/18/medline PY - 2003/8/16/entrez SP - 949 EP - 57 JF - Journal of orthopaedic research : official publication of the Orthopaedic Research Society JO - J Orthop Res VL - 21 IS - 5 N2 - Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. In the present study, we examined whether chemotherapeutic agents enhance TRAIL-induced apoptosis in the sarcoma cell lines MG-63 and SaOS-2. Pretreatment with sub-toxic or slightly toxic concentrations of chemotherapeutic agents (cis-diammine dichloroplatinum, CDDP and doxorubicin, DXR) sensitized both cell lines to TRAIL-induced apoptosis, as assessed by the propidium iodide or Annexin V-Cy5 staining method. These cell lines expressed death receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry. The decoy receptors TRAIL-R3 and -R4 were barely detected in both cell lines. CDDP down-regulated c-FLIP, tending to lower the activation threshold required for TRAIL-induced caspase-8 activation. The CDDP-pretreated cells indeed demonstrated more increased TRAIL-mediated caspase-8 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and apoptosis than untreated cells. Consequently, the activated caspase-8 might lead to either activation of effector caspases such as caspase-3 or loss in DeltaPsi(m). Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS. SN - 0736-0266 UR - https://www.unboundmedicine.com/medline/citation/12919886/Chemotherapeutic_agents_sensitize_sarcoma_cell_lines_to_tumor_necrosis_factor_related_apoptosis_inducing_ligand_induced_caspase_8_activation_apoptosis_and_loss_of_mitochondrial_membrane_potential_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0736026603000627 DB - PRIME DP - Unbound Medicine ER -