Limits...
Cyclic thrombospondin-1 mimetics: grafting of a thrombospondin sequence into circular disulfide-rich frameworks to inhibit endothelial cell migration.

Chan LY, Craik DJ, Daly NL - Biosci. Rep. (2015)

Bottom Line: Importantly, all of the designed cyclic TSP-1 mimetics were far more stable than the linear heptapeptide in human serum.The present study has demonstrated a novel approach to stabilize the active region of TSP-1.The anti-angiogenic activity of the native TSP-1 active fragment was maintained in the new TSP-1 mimetics and the results provide a new chemical approach for the design of TSP-1 mimetics.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, Queensland, Australia.

No MeSH data available.


Related in: MedlinePlus

Cell proliferation assayAll peptides were incubated for 72 h in five different cell lines, including the (A) primary human endothelial cells, (i) HUVECs and (ii) HMVECs, and (B) cancer cells, (i) HT-29, (ii) MCF7 and (iii) PC-3. Each peptide was tested in triplicate and the data represent mean ± S.D.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4660582&req=5

Figure 4: Cell proliferation assayAll peptides were incubated for 72 h in five different cell lines, including the (A) primary human endothelial cells, (i) HUVECs and (ii) HMVECs, and (B) cancer cells, (i) HT-29, (ii) MCF7 and (iii) PC-3. Each peptide was tested in triplicate and the data represent mean ± S.D.

Mentions: Although the cyclic TSP-1 mimetics showed significant inhibition in the endothelial cell migration assay, it was important to confirm that this activity was not an artefact of cell toxicity. Hence the toxicity of the peptides was screened against primary human cells (HUVECs and HMVECs) and selected cancer cell lines (HT-29, MCF-7 and PC-3). None of the peptides affected cell viability during a 2-h incubation (results not shown), which eliminates the possibility that peptide toxicity causes inhibition of cell migration. To evaluate the effect of these peptides on cells that were in a proliferative state, a longer incubation period was also tested. When the peptides were incubated with cells for up to 72 h, none of the peptides had an effect on HUVECs but a minor decrease in cell viability was observed on HMVECs, HT-29, MCF-7 and PC-3 cells, with IC50 values of more than 50 μM (Figures 4A and 4B), indicating that these peptides did not confer a strong reduction on cell viability in these cell lines.


Cyclic thrombospondin-1 mimetics: grafting of a thrombospondin sequence into circular disulfide-rich frameworks to inhibit endothelial cell migration.

Chan LY, Craik DJ, Daly NL - Biosci. Rep. (2015)

Cell proliferation assayAll peptides were incubated for 72 h in five different cell lines, including the (A) primary human endothelial cells, (i) HUVECs and (ii) HMVECs, and (B) cancer cells, (i) HT-29, (ii) MCF7 and (iii) PC-3. Each peptide was tested in triplicate and the data represent mean ± S.D.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660582&req=5

Figure 4: Cell proliferation assayAll peptides were incubated for 72 h in five different cell lines, including the (A) primary human endothelial cells, (i) HUVECs and (ii) HMVECs, and (B) cancer cells, (i) HT-29, (ii) MCF7 and (iii) PC-3. Each peptide was tested in triplicate and the data represent mean ± S.D.
Mentions: Although the cyclic TSP-1 mimetics showed significant inhibition in the endothelial cell migration assay, it was important to confirm that this activity was not an artefact of cell toxicity. Hence the toxicity of the peptides was screened against primary human cells (HUVECs and HMVECs) and selected cancer cell lines (HT-29, MCF-7 and PC-3). None of the peptides affected cell viability during a 2-h incubation (results not shown), which eliminates the possibility that peptide toxicity causes inhibition of cell migration. To evaluate the effect of these peptides on cells that were in a proliferative state, a longer incubation period was also tested. When the peptides were incubated with cells for up to 72 h, none of the peptides had an effect on HUVECs but a minor decrease in cell viability was observed on HMVECs, HT-29, MCF-7 and PC-3 cells, with IC50 values of more than 50 μM (Figures 4A and 4B), indicating that these peptides did not confer a strong reduction on cell viability in these cell lines.

Bottom Line: Importantly, all of the designed cyclic TSP-1 mimetics were far more stable than the linear heptapeptide in human serum.The present study has demonstrated a novel approach to stabilize the active region of TSP-1.The anti-angiogenic activity of the native TSP-1 active fragment was maintained in the new TSP-1 mimetics and the results provide a new chemical approach for the design of TSP-1 mimetics.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, Queensland, Australia.

No MeSH data available.


Related in: MedlinePlus