| Title |
Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells
|
|---|---|
| Published in |
Investigational New Drugs, June 2018
|
| DOI | 10.1007/s10637-018-0620-y |
| Pubmed ID | |
| Authors |
Viviane A. O. Silva, Marcela N. Rosa, Vera Miranda-Gonçalves, Angela M. Costa, Aline Tansini, Adriane F. Evangelista, Olga Martinho, Adriana C. Carloni, Chris Jones, João Paulo Lima, Luiz F. Pianowski, Rui Manuel Reis |
| Abstract |
Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 50% |
| United States | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 57 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 11% |
| Student > Bachelor | 6 | 11% |
| Student > Doctoral Student | 5 | 9% |
| Researcher | 5 | 9% |
| Student > Ph. D. Student | 5 | 9% |
| Other | 10 | 18% |
| Unknown | 20 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 14% |
| Biochemistry, Genetics and Molecular Biology | 6 | 11% |
| Medicine and Dentistry | 6 | 11% |
| Chemistry | 4 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
| Other | 6 | 11% |
| Unknown | 24 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 8. 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 10 August 2023.
All research outputs
#4,626,555
of 25,312,451 outputs
Outputs from Investigational New Drugs
#156
of 1,263 outputs
Outputs of similar age
#81,635
of 335,927 outputs
Outputs of similar age from Investigational New Drugs
#5
of 15 outputs
Altmetric has tracked 25,312,451 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,263 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done well, scoring higher than 87% of its peers.
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We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.