Pro-apoptotic interactions between XK469 and the peripheral benzodiazepinereceptor

XK469 (2-[4-(7-chloro-2-quinoxalinyloxy) phenoxy]propionic acid) is a new a nti-tumor agent with substantial activity against several drug-resistant ce ll 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((R)) was essentially inactive. The cytot oxic response to these agents was accompanied by apoptosis, and was found t o 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. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.