Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis.
Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.
Ondrousková
Eva
E
Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlárská 2, 611 37 Brno, Czech Republic. zahradka@sci.muni.cz
Soucek
Karel
K
Horváth
Viktor
V
Smarda
Jan
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002645:Chickens; D003513:Cycloheximide / Q000494:pharmacology; D020570:Genes, myb / Q000502:physiology; D006801:Humans; D008856:Microscopy, Fluorescence; D009336:Necrosis; D010087:Oxides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D020298:U937 Cells / Q000187:drug effects
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D003513:Cycloheximide; D020169:Caspases; D000077237:Arsenic Trioxide; D002166:Camptothecin