Document Detail

Cathepsin B facilitates autophagy-mediated apoptosis in SPARC overexpressed primitive neuroectodermal tumor cells.
MedLine Citation:
PMID:  20339379     Owner:  NLM     Status:  MEDLINE    
Medulloblastoma and neuroblastoma belong to a group of neoplasms designated as primitive neuroectodermal tumors (PNETs). Secreted protein, acidic and rich in cysteine (SPARC) is a matrix-associated glycoprotein that influences a variety of cellular activities in vitro and in vivo. In this study, we provide evidence that expression of SPARC cDNA induces autophagy in PNET cells followed by apoptotic cell death. SPARC-induced autophagy was morphologically characterized by (i) the formation of membrane-bound autophagic vacuoles (AVOs), (ii) increase in the levels of microtubule-associated protein light chain 3 (LC3) and (iii) induction of the lysososmal enzyme cathepsin B. Cathepsin B, in turn induced mitochondrial release of cytochrome c and activated caspase-3, events that signify the onset of apoptotic cell death. In agreement with these observations, inhibition of autophagy by 3-MA reduced AVO formation and LC3 and inhibited apoptosis, suggesting that autophagy has a role in SPARC-mediated apoptosis. Blocking cathepsin B expression with a specific inhibitor of cathepsin B suppressed apoptosis but did not affect autophagy, which suggests that cathepsin B is a molecular link between autophagy and apoptosis. In summary, these findings show that SPARC expression induces autophagy, which results in the elevation of cathepsin B and subsequent mitochondria-mediated apoptosis.
P Bhoopathi; C Chetty; M Gujrati; D H Dinh; J S Rao; S Lakka
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-03-26
Journal Detail:
Title:  Cell death and differentiation     Volume:  17     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2011-01-04     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1529-39     Citation Subset:  IM    
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MeSH Terms
Caspase 3 / metabolism
Cathepsin B / metabolism*
Cytochromes c / metabolism
Mice, Nude
Microtubule-Associated Proteins / metabolism
Mitochondria / enzymology,  metabolism
Neuroectodermal Tumors, Primitive / metabolism*
Osteonectin / genetics,  metabolism*
RNA Interference
RNA, Small Interfering / metabolism
Tumor Cells, Cultured
Grant Support
R01 CA132853/CA/NCI NIH HHS; R01 CA132853-03/CA/NCI NIH HHS; R01 CA132853-04/CA/NCI NIH HHS
Reg. No./Substance:
0/Microtubule-Associated Proteins; 0/Osteonectin; 0/RNA, Small Interfering; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3; EC B

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