Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines

Lidija Klampfer, Jörg Cammenga, Hans Georg Wisniewski, Stephen D Nimer

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Nonsteroidal antiinflammatory agents (NSAIA) have been shown to exert potent chemopreventive activity against colon, lung, and breast cancers. In this study, we show that at pharmacological concentrations (1 to 3 mmol/L) sodium salicylate (Na-Sal) can potently induce programmed cell death in several human myeloid leukemia cell lines, including TF-1, U937, CMK-1, HL- 60, and Mo7e. TF-1 cells undergo rapid apoptosis on treatment with Na-Sal, as indicated by increased annexin V binding capacity, cpp-32 (caspase-3) activation, and cleavage of poly (ADP-ribose) polymerase (PARP) and gelsolin. In addition, the expression of MCL-1, an antiapoptotic member of the BCL-2 family, is downregulated during Na-Sal-induced cell death, whereas the expression of BCL-2, BAX, and BCL-X(L) is unchanged. Z-VAD, a potent caspase inhibitor, prevents the cleavage of PARP and gelsolin and rescues cells from Na-Sal-induced apoptosis. In addition, we show that Na-Sal accelerates growth factor withdrawal-induced apoptosis and synergizes with daunorubicin to induce apoptosis in TF-1 cells. Thus, our data provide a potential mechanism for the chemopreventive activity of NSAIA and suggest that salicylates may have therapeutic potential for the treatment of human leukemia.

Original languageEnglish
Pages (from-to)2386-2394
Number of pages9
JournalBlood
Volume93
Issue number7
StatePublished - Apr 1 1999
Externally publishedYes

Fingerprint

Sodium Salicylate
Myeloid Leukemia
Myeloid Cells
Caspases
Cells
Gelsolin
Apoptosis
Cell Line
Poly(ADP-ribose) Polymerases
Non-Steroidal Anti-Inflammatory Agents
Cell death
Cell Death
Daunorubicin
Caspase Inhibitors
Salicylates
Annexin A5
Caspase 3
Colonic Neoplasms
Lung Neoplasms
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Klampfer, L., Cammenga, J., Wisniewski, H. G., & Nimer, S. D. (1999). Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood, 93(7), 2386-2394.

Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. / Klampfer, Lidija; Cammenga, Jörg; Wisniewski, Hans Georg; Nimer, Stephen D.

In: Blood, Vol. 93, No. 7, 01.04.1999, p. 2386-2394.

Research output: Contribution to journalArticle

Klampfer, L, Cammenga, J, Wisniewski, HG & Nimer, SD 1999, 'Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines', Blood, vol. 93, no. 7, pp. 2386-2394.
Klampfer L, Cammenga J, Wisniewski HG, Nimer SD. Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood. 1999 Apr 1;93(7):2386-2394.
Klampfer, Lidija ; Cammenga, Jörg ; Wisniewski, Hans Georg ; Nimer, Stephen D. / Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. In: Blood. 1999 ; Vol. 93, No. 7. pp. 2386-2394.
@article{ac43cc2e647945f4ada72701bfebb4c0,
title = "Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines",
abstract = "Nonsteroidal antiinflammatory agents (NSAIA) have been shown to exert potent chemopreventive activity against colon, lung, and breast cancers. In this study, we show that at pharmacological concentrations (1 to 3 mmol/L) sodium salicylate (Na-Sal) can potently induce programmed cell death in several human myeloid leukemia cell lines, including TF-1, U937, CMK-1, HL- 60, and Mo7e. TF-1 cells undergo rapid apoptosis on treatment with Na-Sal, as indicated by increased annexin V binding capacity, cpp-32 (caspase-3) activation, and cleavage of poly (ADP-ribose) polymerase (PARP) and gelsolin. In addition, the expression of MCL-1, an antiapoptotic member of the BCL-2 family, is downregulated during Na-Sal-induced cell death, whereas the expression of BCL-2, BAX, and BCL-X(L) is unchanged. Z-VAD, a potent caspase inhibitor, prevents the cleavage of PARP and gelsolin and rescues cells from Na-Sal-induced apoptosis. In addition, we show that Na-Sal accelerates growth factor withdrawal-induced apoptosis and synergizes with daunorubicin to induce apoptosis in TF-1 cells. Thus, our data provide a potential mechanism for the chemopreventive activity of NSAIA and suggest that salicylates may have therapeutic potential for the treatment of human leukemia.",
author = "Lidija Klampfer and J{\"o}rg Cammenga and Wisniewski, {Hans Georg} and Nimer, {Stephen D}",
year = "1999",
month = "4",
day = "1",
language = "English",
volume = "93",
pages = "2386--2394",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

TY - JOUR

T1 - Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines

AU - Klampfer, Lidija

AU - Cammenga, Jörg

AU - Wisniewski, Hans Georg

AU - Nimer, Stephen D

PY - 1999/4/1

Y1 - 1999/4/1

N2 - Nonsteroidal antiinflammatory agents (NSAIA) have been shown to exert potent chemopreventive activity against colon, lung, and breast cancers. In this study, we show that at pharmacological concentrations (1 to 3 mmol/L) sodium salicylate (Na-Sal) can potently induce programmed cell death in several human myeloid leukemia cell lines, including TF-1, U937, CMK-1, HL- 60, and Mo7e. TF-1 cells undergo rapid apoptosis on treatment with Na-Sal, as indicated by increased annexin V binding capacity, cpp-32 (caspase-3) activation, and cleavage of poly (ADP-ribose) polymerase (PARP) and gelsolin. In addition, the expression of MCL-1, an antiapoptotic member of the BCL-2 family, is downregulated during Na-Sal-induced cell death, whereas the expression of BCL-2, BAX, and BCL-X(L) is unchanged. Z-VAD, a potent caspase inhibitor, prevents the cleavage of PARP and gelsolin and rescues cells from Na-Sal-induced apoptosis. In addition, we show that Na-Sal accelerates growth factor withdrawal-induced apoptosis and synergizes with daunorubicin to induce apoptosis in TF-1 cells. Thus, our data provide a potential mechanism for the chemopreventive activity of NSAIA and suggest that salicylates may have therapeutic potential for the treatment of human leukemia.

AB - Nonsteroidal antiinflammatory agents (NSAIA) have been shown to exert potent chemopreventive activity against colon, lung, and breast cancers. In this study, we show that at pharmacological concentrations (1 to 3 mmol/L) sodium salicylate (Na-Sal) can potently induce programmed cell death in several human myeloid leukemia cell lines, including TF-1, U937, CMK-1, HL- 60, and Mo7e. TF-1 cells undergo rapid apoptosis on treatment with Na-Sal, as indicated by increased annexin V binding capacity, cpp-32 (caspase-3) activation, and cleavage of poly (ADP-ribose) polymerase (PARP) and gelsolin. In addition, the expression of MCL-1, an antiapoptotic member of the BCL-2 family, is downregulated during Na-Sal-induced cell death, whereas the expression of BCL-2, BAX, and BCL-X(L) is unchanged. Z-VAD, a potent caspase inhibitor, prevents the cleavage of PARP and gelsolin and rescues cells from Na-Sal-induced apoptosis. In addition, we show that Na-Sal accelerates growth factor withdrawal-induced apoptosis and synergizes with daunorubicin to induce apoptosis in TF-1 cells. Thus, our data provide a potential mechanism for the chemopreventive activity of NSAIA and suggest that salicylates may have therapeutic potential for the treatment of human leukemia.

UR - http://www.scopus.com/inward/record.url?scp=0033121186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033121186&partnerID=8YFLogxK

M3 - Article

C2 - 10090950

AN - SCOPUS:0033121186

VL - 93

SP - 2386

EP - 2394

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -