BAMLET Activates a Lysosomal Cell Death Program in Cancer Cells
| العنوان: | BAMLET Activates a Lysosomal Cell Death Program in Cancer Cells |
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| المؤلفون: | Jakob E. Larsen, Paul Rammer, Maria Høyer-Hansen, Thomas Kirkegaard, Lou Klitgaard Povlsen, Marja Jäättelä, Mads Daugaard, Piotr Szyniarowski, Jesper Nylandsted, Anna Rytter, Line Groth-Pedersen |
| المصدر: | Molecular Cancer Therapeutics. 9:24-32 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Cancer Research, Programmed cell death, medicine.medical_treatment, Oleic Acids, Mice, Cell Line, Tumor, Neoplasms, Autophagy, medicine, Animals, Humans, Cytotoxic T cell, HSP70 Heat-Shock Proteins, Caspase, bcl-2-Associated X Protein, Cell Death, biology, Growth factor, Caspase Inhibitors, Cell biology, Cytosol, Oncology, Biochemistry, Cytoprotection, Cell culture, Cancer cell, Lactalbumin, biology.protein, Intercellular Signaling Peptides and Proteins, Cattle, Drug Screening Assays, Antitumor, Lysosomes, Oleic Acid, Signal Transduction |
| الوصف: | A complex of human α-lactalbumin and oleic acid (HAMLET) was originally isolated from human milk as a potent anticancer agent. It kills a wide range of transformed cells of various origins while leaving nontransformed healthy cells largely unaffected both in vitro and in vivo. Importantly, purified α-lactalbumins from other mammals form complexes with oleic acid that show biological activities similar to that of HAMLET. The mechanism by which these protein-lipid complexes kill tumor cells is, however, largely unknown. Here, we show that complex of bovine α-lactalbumin and oleic acid (BAMLET), the bovine counterpart of HAMLET, kills tumor cells via a mechanism involving lysosomal membrane permeabilization. BAMLET shows potent cytotoxic activity against eight cancer cell lines tested, whereas nontransformed NIH-3T3 murine embryonic fibroblasts are relatively resistant. BAMLET accumulates rapidly and specifically in the endolysosomal compartment of tumor cells and induces an early leakage of lysosomal cathepsins into the cytosol followed by the activation of the proapoptotic protein Bax. Ectopic expression of three proteins known to stabilize the lysosomal compartment, i.e. heat shock protein 70 (Hsp70), Hsp70-2, and lens epithelium-derived growth factor, confer significant protection against BAMLET-induced cell death, whereas the antiapoptotic protein Bcl-2, caspase inhibition, and autophagy inhibition fail to do so. These data indicate that BAMLET triggers lysosomal cell death pathway in cancer cells, thereby clarifying the ability of α-lactalbumin:oleate complexes to kill highly apoptosis-resistant tumor cells. Mol Cancer Ther; 9(1); 24–32 |
| تدمد: | 1538-8514 1535-7163 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3db9c0e8315dedd0df192167d7c3d1c https://doi.org/10.1158/1535-7163.mct-09-0559 |
| رقم الأكسشن: | edsair.doi.dedup.....d3db9c0e8315dedd0df192167d7c3d1c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15388514 15357163 |
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