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Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma cells - synergism with autophagy inhibition

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, April 2017
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Title
Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma cells - synergism with autophagy inhibition
Published in
Journal of Experimental & Clinical Cancer Research, April 2017
DOI 10.1186/s13046-017-0527-z
Pubmed ID
Authors

Bernd Kubista, Thomas Schoefl, Lisa Mayr, Sushilla van Schoonhoven, Petra Heffeter, Reinhard Windhager, Bernhard K. Keppler, Walter Berger

Abstract

Osteosarcoma is the most frequent primary malignant bone tumor. Although survival has distinctly increased due to neoadjuvant chemotherapy in the past, patients with metastatic disease and poor response to chemotherapy still have an adverse prognosis. Hence, development of new therapeutic strategies is still of utmost importance. Anticancer activity of KP46 against osteosarcoma cell models was evaluated as single agent and in combination approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay. Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays. KP46 exerted exceptional anticancer activity at the nanomolar to low micromolar range, depending on the assay format, against all osteosarcoma cell models with minor but significant differences in IC50 values. KP46 treatment of osteosarcoma cells caused rapid loss of cell adhesion, weak cell cycle accumulation in S-phase and later signs of apoptotic cell death. Furthermore, already at sub-cytotoxic concentrations KP46 reduced the migratory potential of osteosarcoma cells and exerted synergistic effects with cisplatin, a standard osteosarcoma chemotherapeutic. Moreover, the gallium compound induced signs of autophagy in osteosarcoma cells. Accordingly, blockade of autophagy by chloroquine but also by the Bcl-2 inhibitor obatoclax increased the cytotoxic activity of KP46 treatment significantly, suggesting autophagy induction as a protective mechanism against KP46. Together, our results identify KP46 as a new promising agent to supplement standard chemotherapy and possible future targeted therapy in osteosarcoma.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 21%
Student > Bachelor 5 13%
Student > Master 4 11%
Researcher 3 8%
Other 2 5%
Other 5 13%
Unknown 11 29%
Readers by discipline Count As %
Chemistry 6 16%
Medicine and Dentistry 5 13%
Agricultural and Biological Sciences 4 11%
Biochemistry, Genetics and Molecular Biology 4 11%
Immunology and Microbiology 2 5%
Other 5 13%
Unknown 12 32%

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 14 April 2017.
All research outputs
#8,450,313
of 9,689,121 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#405
of 570 outputs
Outputs of similar age
#221,174
of 263,539 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#10
of 11 outputs
Altmetric has tracked 9,689,121 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 570 research outputs from this source. They receive a mean Attention Score of 2.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,539 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.