title: Cathepsins and BID are involved in the molecular switch between apoptosis and autophagy in breast cancer MCF-7 cells exposed to camptothecin.
abstract: The details of molecular switching points between apoptosis and autophagy in tumor cells have still not been fully elucidated. This study focused on the role of cathepsin B and its substrate, BID as molecular links between apoptosis and autophagy in human breast cancer MCF-7 cells exposed to camptothecin. Apoptosis occurred rapidly with a peak in 60 min after drug administration, whereas autophagy developed at a much slower rate with continuous progression during 24 h of cell exposure to the drug. CPT induced very rapid activation of cathepsin B. Inhibition of cathepsins by E64d prevented CPT-induced BAX and BID aggregation on mitochondria and reduced significantly reduced apoptotic cell number. The above effects were accompanied by an increase in autophagosome formation, measured by expression of MAP I LC3. BID knock down resulted in strong suppression of CPT-induced apoptosis and a shift of cell death towards autophagy, manifesting with an increase of Beclin 1 and MAP I LC3 cellular content.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Lamparska-Przybysz
authors.forename: B
authors.initials: B
authors.lastname: Gajkowska
authors.forename: T
authors.initials: T
authors.lastname: Motyl
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D002166:Camptothecin / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007700:Kinetics; D047569:Laser Scanning Cytometry; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C491997:BECN1 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000071186:Beclin-1; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D051028:bcl-2-Associated X Protein; D002401:Cathepsin B; D007930:Leucine; C108192:aloxistatin; D002166:Camptothecin