PMID- 17180102 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121002 LR - 20061220 IS - 1350-9047 (Print) IS - 1350-9047 (Linking) VI - 3 IP - 3 DP - 1996 Jul TI - Imidazole antifungals Miconazole and Econazole induce apoptosis in mouse lymphoma and human T cell leukemia cells: regulation by Bcl-2 and potential role of calcium. PG - 331-7 AB - We have recently reported that thapsigargin (TG), a specific endoplasmic reticulum (ER)-associated Ca(2+)-ATPase inhibitor, induces apoptosis in mouse lymphoma cells. In view of recent evidence that the imidazole antifungals econazole (EC) and miconazole (MC) inhibit TG-sensitive Ca(2+)-ATPase activity in normal rat thymocytes, we investigated the effect of these agents on intracellular Ca(2+) homeostasis and cell survival in WEHI7.2 mouse lymphoma cells and human CEMT-cell leukemia cells. In this report, we demonstrate that MC treatment releases Ca(2+) from the TG-sensitive ER pool of WEHI7.2 cells. MC induced apoptosis, based on morphological and biochemical criteria, and on inhibition by the Bcl-2 oncogene. Moreover, intracellular Ca(2+) changes induced by MC treatment were inhibited by overexpression of Bcl-2. In addition to inducing cell death in WEHI7.2 cells, MC induced apoptosis in the glucocorticoid sensitive and resistant human T-cell leukemia lines, CEM-C7 and CEM-C1 respectively, in normal thymocytes and in normal lymphocytes. Based on their apoptosis-inducing activity, imidazole derivatives should be explored as potential immunosuppressive and/or chemotherapeutic agents. FAU - Sobecks, R AU - Sobecks R AD - Departments of Medicine and Pharmacology, Case Western Reserve University, Cleveland, Ohio. FAU - McCormick, T S AU - McCormick TS FAU - Distelhorst, C W AU - Distelhorst CW LA - eng PT - Journal Article PL - England TA - Cell Death Differ JT - Cell death and differentiation JID - 9437445 EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 CRDT- 1996/07/01 00:00 PHST- 1995/12/12 00:00 [received] PHST- 1996/02/22 00:00 [revised] PHST- 1996/03/11 00:00 [accepted] PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] PST - ppublish SO - Cell Death Differ. 1996 Jul;3(3):331-7.