PMID- 27551514
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160823
LR  - 20200930
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 2
DP  - 2016
TI  - Cytotoxic L-amino-acid oxidases from Amanita phalloides and Clitocybe geotropa 
      induce caspase-dependent apoptosis.
PG  - 16021
LID - 10.1038/cddiscovery.2016.21 [doi]
AB  - L-amino-acid oxidases (LAO) purified from fungi induce cell death in various 
      mammalian cells including human tumor cell lines. The mechanism, however, remains 
      poorly understood. In this study, we aimed to define a precise mechanism of cell 
      death induced in Jurkat and MCF7 cancer cell lines by ApLAO and CgLAO, LAOs 
      isolated from Amanita phalloides and Clitocybe geotropa, respectively. Cell death 
      induced by both LAOs is shown to be concentration- and time-dependent, with 
      higher toxic effects in Jurkat cells. LAO activity is required for the 
      cytotoxicity. Detailed study on Jurkat cells further demonstrated that ApLAO and 
      CgLAO both induce the intrinsic mitochondrial pathway of apoptosis, accompanied 
      by a time-dependent depolarization of the mitochondrial membrane through the 
      generation of reactive oxygen species. Treatment with the LAOs resulted in an 
      increased ratio of the expression of proapoptotic Bax to that of antiapoptotic 
      Bcl-2, subsequently leading to the activation of caspase-9 and -3. However, the 
      pancaspase inhibitor, Z-VAD-FMK, did not completely abolish the cell death 
      induced by either ApLAO or CgLAO, suggesting an alternative pathway for 
      LAO-induced apoptosis. Indeed, caspase-8 activity in ApLAO- and CgLAO-treated 
      cells was increased. Further, Fas/FasL (Fas ligand) antagonist caused a slight 
      reduction in toxin-induced cell death, supporting the involvement of ApLAO and 
      CgLAO in death-receptor-mediated apoptosis. These results thus provide new 
      evidence that ApLAO and CgLAO induce apoptosis in Jurkat cells via both the 
      intrinsic and extrinsic pathways, although the significantly higher increase of 
      caspase-9 over caspase-8 activity suggests that it is the intrinsic pathway that 
      is the predominant mode of ApLAO- and CgLAO-induced apoptosis.
FAU - Pislar, A
AU  - Pislar A
AD  - Department of Pharmaceutical Biology, Faculty of Pharmacy, University of 
      Ljubljana , Askerceva 7, 1000 Ljubljana, Slovenia.
FAU - Sabotic, J
AU  - Sabotic J
AD  - Department of Biotechnology, Jozef Stefan Institute , Jamova cesta 39, 1000 
      Ljubljana, Slovenia.
FAU - Slenc, J
AU  - Slenc J
AD  - Department of Pharmaceutical Biology, Faculty of Pharmacy, University of 
      Ljubljana , Askerceva 7, 1000 Ljubljana, Slovenia.
FAU - Brzin, J
AU  - Brzin J
AD  - Department of Biotechnology, Jozef Stefan Institute , Jamova cesta 39, 1000 
      Ljubljana, Slovenia.
FAU - Kos, J
AU  - Kos J
AD  - Department of Pharmaceutical Biology, Faculty of Pharmacy, University of 
      Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia; Department of Biotechnology, 
      Jozef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
DEP - 20160321
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC4979486
EDAT- 2016/08/24 06:00
MHDA- 2016/08/24 06:01
PMCR- 2016/03/21
CRDT- 2016/08/24 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/02/05 00:00 [revised]
PHST- 2016/02/14 00:00 [accepted]
PHST- 2016/08/24 06:00 [entrez]
PHST- 2016/08/24 06:00 [pubmed]
PHST- 2016/08/24 06:01 [medline]
PHST- 2016/03/21 00:00 [pmc-release]
AID - cddiscovery201621 [pii]
AID - 10.1038/cddiscovery.2016.21 [doi]
PST - epublish
SO  - Cell Death Discov. 2016 Mar 21;2:16021. doi: 10.1038/cddiscovery.2016.21. 
      eCollection 2016.