期刊
CANCER LETTERS
卷 249, 期 2, 页码 294-299出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2006.09.009
关键词
apoptosis; autophagy; Bcl-2; HA14-1; vacuoles; L1210
类别
资金
- NCI NIH HHS [R01 CA023378-24, R01 CA023378, CA 23378, R01 CA023378-29, R01 CA023378-28] Funding Source: Medline
L1210 murine leukemia cells exposed to an LD90 concentration of the Bcl-2/Bcl-x(L) antagonist HA14-1 rapidly undergo apoptosis but also develop numerous intracellular vacuoles with double membranes, exhibit enhanced labeling by monodansylcadaverine, and convert the cytosolic protein LC3-I to LC3-II. These are hallmarks of autophagy. Autophagic vacnotes develop rapidly, preceding the appearance of an apoptotic nuclear morphology and can be observed in both non-apoptotic and apoptotic cells. Inhibition of autophagy by the PI 3-kinase inhibitor wortmannin promoted apoptosis; conversely inhibition of caspase-3/7 with zDEVD-fmk promoted autophagy. Neither process was dependent on calcium translocation. These results indicate that pharmacological suppression of Bcl-2 function can mimic the induction of autophagy that can occur following the down-regulation of Bcl-2 expression by molecular approaches. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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