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Role of tumor necrosis factor alpha in hyperthermia-induced apoptosis of human leukemia cells.
Cancer Res. 1999 Jul 15; 59(14):3404-10.CR

Abstract

We used the human myelomonoblastic leukemia cell line PLB-985 to study the effects of temperatures ranging from 37 degrees C to 43 degrees C for 1 h on the induction of apoptosis and cell cycle distribution in leukemia cells. The threshold temperature for the onset of apoptosis was 42 degrees C. Whereas hyperthermia exerted no effect on the expression of Bcl-2 and Bax, heat induced a >30-fold increase of tumor necrosis factor (TNF) alpha mRNA expression and a significant increase in TNF-alpha protein secretion. This endogenous production of TNF-alpha correlated directly with the temperature-induced apoptode effect. Blocking TNF-alpha expression via treatment with pyrrolidinedithiocarbamate or blocking TNF-alpha activity with neutralizing antibodies abrogated heat-provoked apoptosis. In addition, exposure of cell culture supernatant of heat-treated PLB-985 cells to untreated cells induced an apoptotic effect. These data indicate a TNF-a-mediated self eradication of the leukemia cells after heat exposure. Inducing apoptosis with wild-type TNF-alpha or p55 and p75 protein muteins demonstrated that this effect was mediated by the p55 receptor. Interestingly, the autocrine suicidal loop found in immature leukemia cells was lost after granulocytic differentiation with 0.5% N,N-dimethylformamide. These data should be of critical importance for the understanding of the biological impact of fever as well as for developing therapeutic approaches to malignant diseases

Authors+Show Affiliations

Institute of Physiology, Medical University of Lübeck, Germany. katschinski@physio.mu-luebeck.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10416602

Citation

Katschinski, D M., et al. "Role of Tumor Necrosis Factor Alpha in Hyperthermia-induced Apoptosis of Human Leukemia Cells." Cancer Research, vol. 59, no. 14, 1999, pp. 3404-10.
Katschinski DM, Robins HI, Schad M, et al. Role of tumor necrosis factor alpha in hyperthermia-induced apoptosis of human leukemia cells. Cancer Res. 1999;59(14):3404-10.
Katschinski, D. M., Robins, H. I., Schad, M., Frede, S., & Fandrey, J. (1999). Role of tumor necrosis factor alpha in hyperthermia-induced apoptosis of human leukemia cells. Cancer Research, 59(14), 3404-10.
Katschinski DM, et al. Role of Tumor Necrosis Factor Alpha in Hyperthermia-induced Apoptosis of Human Leukemia Cells. Cancer Res. 1999 Jul 15;59(14):3404-10. PubMed PMID: 10416602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of tumor necrosis factor alpha in hyperthermia-induced apoptosis of human leukemia cells. AU - Katschinski,D M, AU - Robins,H I, AU - Schad,M, AU - Frede,S, AU - Fandrey,J, PY - 1999/7/23/pubmed PY - 1999/7/23/medline PY - 1999/7/23/entrez SP - 3404 EP - 10 JF - Cancer research JO - Cancer Res. VL - 59 IS - 14 N2 - We used the human myelomonoblastic leukemia cell line PLB-985 to study the effects of temperatures ranging from 37 degrees C to 43 degrees C for 1 h on the induction of apoptosis and cell cycle distribution in leukemia cells. The threshold temperature for the onset of apoptosis was 42 degrees C. Whereas hyperthermia exerted no effect on the expression of Bcl-2 and Bax, heat induced a >30-fold increase of tumor necrosis factor (TNF) alpha mRNA expression and a significant increase in TNF-alpha protein secretion. This endogenous production of TNF-alpha correlated directly with the temperature-induced apoptode effect. Blocking TNF-alpha expression via treatment with pyrrolidinedithiocarbamate or blocking TNF-alpha activity with neutralizing antibodies abrogated heat-provoked apoptosis. In addition, exposure of cell culture supernatant of heat-treated PLB-985 cells to untreated cells induced an apoptotic effect. These data indicate a TNF-a-mediated self eradication of the leukemia cells after heat exposure. Inducing apoptosis with wild-type TNF-alpha or p55 and p75 protein muteins demonstrated that this effect was mediated by the p55 receptor. Interestingly, the autocrine suicidal loop found in immature leukemia cells was lost after granulocytic differentiation with 0.5% N,N-dimethylformamide. These data should be of critical importance for the understanding of the biological impact of fever as well as for developing therapeutic approaches to malignant diseases SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/10416602/Role_of_tumor_necrosis_factor_alpha_in_hyperthermia_induced_apoptosis_of_human_leukemia_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10416602 DB - PRIME DP - Unbound Medicine ER -