serval:BIB_F2DA0AC290B8
The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner.
10.18632/oncotarget.11841
000387167800120
27602963
Heulot
M.
author
Chevalier
N.
author
Puyal
J.
author
Margue
C.
author
Michel
S.
author
Kreis
S.
author
Kulms
D.
author
Barras
D.
author
Nahimana
A.
author
Widmann
C.
author
article
2016-09-27
Oncotarget
1949-2553
1949-2553
journal
7
39
64342-64359
Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments. Recently, we discovered that this RasGAP-derived peptide possesses the ability to directly kill some cancer cells. TAT-RasGAP317-326 can cause cell death in a manner that can be either partially caspase-dependent or fully caspase-independent. Indeed, TAT-RasGAP317-326-induced toxicity was not or only partially prevented when apoptosis was inhibited. Moreover, blocking other forms of cell death, such as necroptosis, parthanatos, pyroptosis and autophagy did not hamper the killing activity of the peptide. The death induced by TAT-RasGAP317-326 can therefore proceed independently from these modes of death. Our finding has potentially interesting clinical relevance because activation of a death pathway that is distinct from apoptosis and necroptosis in tumor cells could lead to the generation of anti-cancer drugs that target pathways not yet considered for cancer treatment.
Animals
Antineoplastic Agents/pharmacology
Apoptosis/drug effects
Caspase Inhibitors/pharmacology
Caspases/genetics
Caspases/metabolism
Cell Line, Tumor
Cercopithecus aethiops
Dose-Response Relationship, Drug
Female
GTPase-Activating Proteins/pharmacology
HEK293 Cells
Humans
Male
Necrosis
Neoplasms/drug therapy
Neoplasms/genetics
Neoplasms/metabolism
Neoplasms/pathology
Peptide Fragments/pharmacology
Signal Transduction/drug effects
Time Factors
Vero Cells
RasGAP
cell-permeable peptides
non-apoptotic death
tumor cell death
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: ppublish
University of Lausanne
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