| Title |
PRIMA-1MET induces death in soft-tissue sarcomas cell independent of p53
|
|---|---|
| Published in |
BMC Cancer, October 2015
|
| DOI | 10.1186/s12885-015-1667-1 |
| Pubmed ID | |
| Authors |
Thomas Grellety, Audrey Laroche-Clary, Vanessa Chaire, Pauline Lagarde, Frédéric Chibon, Agnes Neuville, Antoine Italiano |
| Abstract |
The aim of this study was to explore the efficacy and define mechanisms of action of PRIMA-1(MET) as a TP53 targeted therapy in soft-tissue sarcoma (STS) cells. We investigated effects of PRIMA-1(MET) on apoptosis, cell cycle, and induction of oxidative stress and autophagy in a panel of 6 STS cell lines with different TP53 status. Cell viability reduction by PRIMA-1(MET) was significantly observed in 5 out of 6 STS cell lines. We found that PRIMA-1(MET) was capable to induce cell death not only in STS cells harboring mutated TP53 but also in TP53-null STS cells demonstrating that PRIMA-1(MET) can induce cell death independently of TP53 in STS cells. We identified an important role of reactive oxygen species (ROS), involved in PRIMA-1(MET) toxicity in STS cells leading to a caspase-independent cell death. ROS toxicity was associated with autophagy induction or JNK pathway activation which represented potential mechanisms of cell death induced by PRIMA-1(MET) in STS. PRIMA-1(MET) anti-tumor activity in STS partly results from off-target effects involving ROS toxicity and do not deserve further development as a TP53-targeted therapy in this setting. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 19 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 32% |
| Student > Ph. D. Student | 3 | 16% |
| Student > Master | 2 | 11% |
| Professor | 1 | 5% |
| Lecturer | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 5 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 26% |
| Agricultural and Biological Sciences | 3 | 16% |
| Medicine and Dentistry | 3 | 16% |
| Chemistry | 1 | 5% |
| Unknown | 7 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 October 2015.
All research outputs
#20,294,248
of 22,830,751 outputs
Outputs from BMC Cancer
#6,496
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Outputs of similar age
#234,162
of 279,229 outputs
Outputs of similar age from BMC Cancer
#179
of 234 outputs
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