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Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes.
Biochem Pharmacol. 1994 Nov 16; 48(10):1883-9.BP

Abstract

We examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells.

Authors+Show Affiliations

Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.No affiliation info availableNo affiliation info availableNo 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

7986199

Citation

Bessho, R, et al. "Pyrrolidine Dithiocarbamate, a Potent Inhibitor of Nuclear Factor Kappa B (NF-kappa B) Activation, Prevents Apoptosis in Human Promyelocytic Leukemia HL-60 Cells and Thymocytes." Biochemical Pharmacology, vol. 48, no. 10, 1994, pp. 1883-9.
Bessho R, Matsubara K, Kubota M, et al. Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. Biochem Pharmacol. 1994;48(10):1883-9.
Bessho, R., Matsubara, K., Kubota, M., Kuwakado, K., Hirota, H., Wakazono, Y., Lin, Y. W., Okuda, A., Kawai, M., & Nishikomori, R. (1994). Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. Biochemical Pharmacology, 48(10), 1883-9.
Bessho R, et al. Pyrrolidine Dithiocarbamate, a Potent Inhibitor of Nuclear Factor Kappa B (NF-kappa B) Activation, Prevents Apoptosis in Human Promyelocytic Leukemia HL-60 Cells and Thymocytes. Biochem Pharmacol. 1994 Nov 16;48(10):1883-9. PubMed PMID: 7986199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. A1 - Bessho,R, AU - Matsubara,K, AU - Kubota,M, AU - Kuwakado,K, AU - Hirota,H, AU - Wakazono,Y, AU - Lin,Y W, AU - Okuda,A, AU - Kawai,M, AU - Nishikomori,R, PY - 1994/11/16/pubmed PY - 1994/11/16/medline PY - 1994/11/16/entrez SP - 1883 EP - 9 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 48 IS - 10 N2 - We examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/7986199/Pyrrolidine_dithiocarbamate_a_potent_inhibitor_of_nuclear_factor_kappa_B__NF_kappa_B__activation_prevents_apoptosis_in_human_promyelocytic_leukemia_HL_60_cells_and_thymocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-2952(94)90586-X DB - PRIME DP - Unbound Medicine ER -