Cathepsins and BID are involved in the molecular switch between apoptosis and autophagy in breast cancer MCF-7 cells exposed to camptothecin.
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.
Lamparska-Przybysz
M
M
Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland.
Gajkowska
B
B
Motyl
T
T
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
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