Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent.

Purpose: Imexon is a 2-cyanoaziridine agent that has been shown to inhibit growth of chemotherapy-sensitive myeloma cells through apoptosis with decreased cellular stores of glutathione and increased reactive oxygen species (ROS). We examined the mechanism of imexon cytotoxicity in a diverse panel of dexamethasone and chemotherapy-sensitive and -resistant myeloma cell lines.

Experimental Design: We examined cellular cytotoxicity, apoptosis, and changes in redox state in dexamethasone-sensitive (C2E3), dexamethasone-resistant (1-310 and 1-414), chemotherapy-sensitive (RPMI-8226), and chemotherapy-resistant (DOX-1V and DOX-10V) myeloma cell lines.

Arsenic trioxide cytotoxicity in steroid and chemotherapy-resistant myeloma cell lines: enhancement of apoptosis by manipulation of cellular redox state.

Purpose: We investigated the ability of pretreatment with buthionine sulfoximine (BSO) to overcome a priori resistance to arsenic trioxide (As(2)O(3)) in multiple myeloma (MM) cells and determine whether this was through an apoptotic mechanism that involves changes in the cellular redox state.

Experimental Design: Using a panel of dexamethasone and chemotherapy-resistant MM cell lines, we examined growth inhibition, induction of apoptosis, and changes in the redox state by As(2)O(3) alone or after preincubation with BSO.

Results: Whereas the sensitive cell lines showed 100% killing at 0.