S-Acetyl-Glutathione Selectively Induces Apoptosis in Human Lymphoma Cells Through a GSH-Independent Mechanism
March 14, 2022
Comparative Study
Int J Onco. 2002 Jan;20(1):69-75.
Roberto Locigno 1 , Joel Pincemail, Audrey Henno, Gernot Treusch, Vincent Castronovo
PMID: 11743644
Abstract
Reduced apoptosis is associated to cancer development. Agents able to restore the programmed cell death responsiveness of cancer cells are foreseen as potential effective cancer therapies. In this study, we report that a glutathione-S-derivative, S-acetyl-glutathione (Sag), induces significant apoptosis in three human lymphoma cell lines, including Daudi, Raji and Jurkat cells while it had no or little effect on either Hut-78 lymphoma cells or the normal BT lymphocytes. We used Annexin-V FACS analysis and DNA laddering to demonstrate that Sag activated apoptosis in the three sensitive cell lines in a dose- and time-dependent-fashion. Using mercury orange staining and FACS analysis, we showed that Sag generated an intracellular GSH depletion in Daudi, Raji and Jurkat cells but not in Hut-78 or the normal BT cells. These data provide direct evidence that Sag specifically activates programmed cell death in lymphoma cells through, at least in part, a depletion of intracellular GSH rather than an increase, as previously suggested. Because of its selective effect on cancer cells, Sag appears as a promising new lymphoma cell apoptosis inducer with potential clinical value for lymphoma patients.
Similar articles
Giri U, Terry NH, Kala SV, Lieberman MW, Story MD. Cancer Chemother Pharmacol. 2005 Jun;55(6):511-21. doi: 10.1007/s00280-004-0920-0. Epub 2005 Mar 11. PMID: 15761769
Han YH, Kim SZ, Kim SH, Park WH. Int J Mol Med. 2008 Jun;21(6):721-30. PMID: 18506365
Meurette O, Lefeuvre-Orfila L, Rebillard A, Lagadic-Gossmann D, Dimanche-Boitrel MT. Clin Cancer Res. 2005 Apr 15;11(8):3075-83. doi: 10.1158/1078-0432.CCR-04-1764. PMID: 15837763
Lim KM, Chow VT. Mol Carcinog. 2002 Nov;35(3):110-26. doi: 10.1002/mc.10082. PMID: 12410563
Han YH, Kim SZ, Kim SH, Park WH. Cell Biol Int. 2008 Dec;32(12):1536-45. doi: 10.1016/j.cellbi.2008.08.023. Epub 2008 Aug 30. PMID: 18801451
Publication types
- Comparative Study
- Research Support, Non-U.S. Gov't
MeSH terms
- Annexin A5 / metabolism
- Apoptosis / drug effects*
- DNA, Neoplasm / analysis
- Dose-Response Relationship, Drug
- Flow Cytometry
- Glutathione / analogs & derivatives*
- Glutathione / metabolism*
- Glutathione / pharmacology*
- Humans
- Lymphoma / metabolism
- Lymphoma / pathology*
- Time Factors
- Tumor Cells, Cultured / drug effects
- Tumor Cells, Cultured / metabolism
- Tumor Cells, Cultured / pathology
Substances
- Annexin A5
- DNA, Neoplasm
- S-acetylglutathione
- Glutathione