The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate
Само за регистроване кориснике
2013
Аутори
O'Connor, StephenSzwej, Emilia
Nikodinović-Runić, Jasmina
O'Connor, Aisling
Byrne, Annette T.
Devocelle, Marc
O'Donovan, Norma
Gallagher, William M.
Babu, Ramesh
Kenny, Shane T.
Zinn, Manfred
Zulian, Qun Ren
O'Connor, Kevin
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a D-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a terminally hydroxylated decanoic acid (omega-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC50 values c...ompared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC50 values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC50 values in the nanomolar range.
Кључне речи:
Polyhydroxyalkanoate / Monomer / Cancer biology / Apoptosis / Antimicrobial peptides / (R)-3-hydroxydecanoic acidИзвор:
Biomaterials, 2013, 34, 11, 2710-2718Издавач:
- Elsevier Sci Ltd, Oxford
Финансирање / пројекти:
- Science Foundation Ireland [06/RFP/CHO024/EC07]
- UCD Ad Astra Scholarship Programme
- HEA PRTLI4 (bio) pharmaceutical and pharmacological sciences programme
DOI: 10.1016/j.biomaterials.2012.12.032
ISSN: 0142-9612
PubMed: 23343631
WoS: 000315748200014
Scopus: 2-s2.0-84873085844
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - O'Connor, Stephen AU - Szwej, Emilia AU - Nikodinović-Runić, Jasmina AU - O'Connor, Aisling AU - Byrne, Annette T. AU - Devocelle, Marc AU - O'Donovan, Norma AU - Gallagher, William M. AU - Babu, Ramesh AU - Kenny, Shane T. AU - Zinn, Manfred AU - Zulian, Qun Ren AU - O'Connor, Kevin PY - 2013 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/637 AB - The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a D-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a terminally hydroxylated decanoic acid (omega-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC50 values compared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC50 values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC50 values in the nanomolar range. PB - Elsevier Sci Ltd, Oxford T2 - Biomaterials T1 - The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate EP - 2718 IS - 11 SP - 2710 VL - 34 DO - 10.1016/j.biomaterials.2012.12.032 ER -
@article{ author = "O'Connor, Stephen and Szwej, Emilia and Nikodinović-Runić, Jasmina and O'Connor, Aisling and Byrne, Annette T. and Devocelle, Marc and O'Donovan, Norma and Gallagher, William M. and Babu, Ramesh and Kenny, Shane T. and Zinn, Manfred and Zulian, Qun Ren and O'Connor, Kevin ", year = "2013", abstract = "The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a D-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a terminally hydroxylated decanoic acid (omega-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC50 values compared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC50 values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC50 values in the nanomolar range.", publisher = "Elsevier Sci Ltd, Oxford", journal = "Biomaterials", title = "The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate", pages = "2718-2710", number = "11", volume = "34", doi = "10.1016/j.biomaterials.2012.12.032" }
O'Connor, S., Szwej, E., Nikodinović-Runić, J., O'Connor, A., Byrne, A. T., Devocelle, M., O'Donovan, N., Gallagher, W. M., Babu, R., Kenny, S. T., Zinn, M., Zulian, Q. R.,& O'Connor, K.. (2013). The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate. in Biomaterials Elsevier Sci Ltd, Oxford., 34(11), 2710-2718. https://doi.org/10.1016/j.biomaterials.2012.12.032
O'Connor S, Szwej E, Nikodinović-Runić J, O'Connor A, Byrne AT, Devocelle M, O'Donovan N, Gallagher WM, Babu R, Kenny ST, Zinn M, Zulian QR, O'Connor K. The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate. in Biomaterials. 2013;34(11):2710-2718. doi:10.1016/j.biomaterials.2012.12.032 .
O'Connor, Stephen, Szwej, Emilia, Nikodinović-Runić, Jasmina, O'Connor, Aisling, Byrne, Annette T., Devocelle, Marc, O'Donovan, Norma, Gallagher, William M., Babu, Ramesh, Kenny, Shane T., Zinn, Manfred, Zulian, Qun Ren, O'Connor, Kevin , "The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate" in Biomaterials, 34, no. 11 (2013):2710-2718, https://doi.org/10.1016/j.biomaterials.2012.12.032 . .