Pro-apoptotic interactions between XK469 and the peripheral benzodiazepine receptor.

Abstract

XK469 (2-[4-(7-chloro-2-quinoxalinyloxy) phenoxy]propionic acid) is a new anti-tumor agent with substantial activity against several drug-resistant cell lines. Using murine leukemia L1210 cells in culture, we found the chiral R(+) form of XK469 to be substantially more cytotoxic than the S(-) form, while the herbicide analog 'Assure' was essentially inactive. The cytotoxic response to these agents was accompanied by apoptosis, and was found to be correlated with drug binding to the peripheral benzodiazepine receptor in cell culture, suggesting that receptor binding may be a factor in drug-induced cytotoxicity.

• Authors: D Kessel, J P Horwitz
• Journal: Cancer letters (Cancer Lett) Vol. 168 Issue 2 Pg. 141-4 (Jul 26 2001) ISSN: 0304-3835 [Print] Ireland
• PMID: 11403918 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• GABA-A Receptor Agonists
• Isoquinolines
• Quinoxalines
• Receptors, GABA-A
• XK 469
• Staurosporine
• PK 11195

Topics

• Animals
• Antineoplastic Agents (metabolism, pharmacology)
• Apoptosis (drug effects, physiology)
• Binding, Competitive
• Cell Nucleus (drug effects)
• GABA-A Receptor Agonists
• Intracellular Membranes (drug effects, physiology)
• Isoquinolines (metabolism, pharmacology)
• Leukemia L1210 (drug therapy, pathology)
• Membrane Potentials (drug effects)
• Mice
• Mitochondria (drug effects, physiology)
• Quinoxalines (metabolism, pharmacology)
• Receptors, GABA-A (metabolism)
• Staurosporine (pharmacology)
• Stereoisomerism