PMID- 18935973
OWN - NLM
STAT- MEDLINE
DCOM- 20090813
LR  - 20181201
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 41
IP  - 5
DP  - 2009 May
TI  - Saporin induces multiple death pathways in lymphoma cells with different 
      intensity and timing as compared to ricin.
PG  - 1055-61
LID - 10.1016/j.biocel.2008.09.021 [doi]
AB  - Ribosome-inactivating protein (RIP)-containing immunotoxins are currently used in 
      clinical trials as anti-tumour drugs, in particular against haematological 
      malignancies. In cell killing-based therapies it is important to identify the 
      death pathways induced by the cytotoxic agent. The purpose of this work was to 
      compare the pathways of cell death induced by the RIP saporin with those carried 
      out by ricin in the L540 human Hodgkin's lymphoma-derived cell line. Protein 
      synthesis inhibition, activation of caspases, DNA fragmentation and loss of 
      viability have been evaluated. The two toxins triggered a similar DNA 
      fragmentation and cell death, at concentrations giving the same level of cell 
      protein synthesis inhibition, although the inhibitory effect of ricin on protein 
      synthesis was more rapid than that of saporin. Moreover, the intrinsic apoptotic 
      pathway was equally activated by both toxins, whilst ricin activated the 
      extrinsic caspase pathway and the effector caspase-3/7 more efficiently than 
      saporin. The complete inhibition of caspases by Z-VAD was only partially 
      effective in cell rescue which appeared to be time limited. Necrostatin-1, a new 
      inhibitor of non-apoptotic death, rescued cells from death by RIPs, although the 
      effect was also partial and temporary. Despite the high RIP doses used no 
      necrosis was detectable by Annexin V/Propidium Iodide (PI) test. These results 
      suggest that more than one death mechanism was elicited by both ricin and 
      saporin, however, with different timing and strength. The perspective of 
      modulating cell death of neoplastic lymphocytes through different pathways could 
      add new opportunities to reduce side effects and develop combined synergic 
      immuno-chemotherapy.
FAU - Polito, Letizia
AU  - Polito L
AD  - Dipartimento di Patologia Sperimentale, Alma Mater Studiorum - Universita di 
      Bologna, via San Giacomo 14, I-40126 Bologna, Italy.
FAU - Bortolotti, Massimo
AU  - Bortolotti M
FAU - Farini, Valentina
AU  - Farini V
FAU - Battelli, Maria Giulia
AU  - Battelli MG
FAU - Barbieri, Luigi
AU  - Barbieri L
FAU - Bolognesi, Andrea
AU  - Bolognesi A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080930
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Ribosome Inactivating Proteins, Type 1)
RN  - 9009-86-3 (Ricin)
RN  - EC 3.2.2.22 (Saporins)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis/drug effects
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Hodgkin Disease/*drug therapy/pathology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Ribosome Inactivating Proteins, Type 1/*pharmacology
MH  - Ricin/*pharmacology
MH  - Saporins
EDAT- 2008/10/22 09:00
MHDA- 2009/08/14 09:00
CRDT- 2008/10/22 09:00
PHST- 2008/07/02 00:00 [received]
PHST- 2008/09/19 00:00 [revised]
PHST- 2008/09/24 00:00 [accepted]
PHST- 2008/10/22 09:00 [pubmed]
PHST- 2009/08/14 09:00 [medline]
PHST- 2008/10/22 09:00 [entrez]
AID - S1357-2725(08)00402-0 [pii]
AID - 10.1016/j.biocel.2008.09.021 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2009 May;41(5):1055-61. doi: 
      10.1016/j.biocel.2008.09.021. Epub 2008 Sep 30.