Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines Journal Article
| Authors: | Klampfer, L.; Cammenga, J.; Wisniewski, H. G.; Nimer, S. D. |
| Article 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. |
| Keywords: | controlled study; human cell; drug potentiation; protein bcl 2; cancer prevention; apoptosis; breast cancer; neoplasm proteins; lung cancer; caspase 3; drug potency; enzyme activation; tumor cells, cultured; amino acid chloromethyl ketones; caspases; cysteine proteinase inhibitors; drug synergism; protein processing, post-translational; drug mechanism; colon cancer; nonsteroid antiinflammatory agent; anti-inflammatory agents, non-steroidal; anticarcinogenic agents; leukemia, myeloid; daunorubicin; hematopoietic stem cells; growth factor; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; proto-oncogene proteins c-bcl-2; lipocortin 5; leukemia cell line; gene expression regulation, leukemic; myeloid leukemia; poly(adp-ribose) polymerases; protein bax; k562 cells; granulocyte-macrophage colony-stimulating factor; annexin a5; protein bcl x; gelsolin; sodium salicylate; salicylate sodium; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 93 |
| Issue: | 7 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1999-04-01 |
| Start Page: | 2386 |
| End Page: | 2394 |
| Language: | English |
| PUBMED: | 10090950 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V93.7.2386 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work