Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate

Verena Natalie Schreier, Lilla Petho, Erika Orbán, Andreas Marquardt, Brindusa Alina Petre, G. Mező, Marilena Manea

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Targeted delivery of chemotherapeutic agents is a new approach for the treatment of cancer, which provides increased selectivity and decreased systemic toxicity. We have recently developed a promising drug delivery system, in which the anticancer drug daunorubicin (Dau) was attached via oxime bond to a gonadotropin-releasing hormone-III (GnRH-III) derivative used as a targeting moiety (Glp-His-Trp-Lys(Ac)-His-Asp-Trp-Lys(Dau = Aoa)-Pro-Gly-NH2; Glp = pyroglutamic acid, Ac = acetyl; Aoa = aminooxyacetyl). This bioconjugate exerted in vitro cytostatic/cytotoxic effect on human breast, prostate and colon cancer cells, as well as significant in vivo tumor growth inhibitory effect on colon carcinoma bearing mice. In our previous studies, H-Lys(Dau = Aoa)-OH was identified as the smallest metabolite produced in the presence of rat liver lysosomal homogenate, which was able to bind to DNA in vitro. To get a deeper insight into the mechanism of action of the bioconjugate, changes in the protein expression profile of HT-29 human colon cancer cells after treatment with the bioconjugate or free daunorubicin were investigated by mass spectrometry-based proteomics. Our results indicate that several metabolism-related proteins, molecular chaperons and proteins involved in signaling are differently expressed after targeted chemotherapeutic treatment, leading to the conclusion that the bioconjugate exerts its cytotoxic action by interfering with multiple intracellular processes.

Original languageEnglish
Article numbere94041
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 9 2014

Fingerprint

daunorubicin
Daunorubicin
gonadotropin-releasing hormone
colorectal neoplasms
Colonic Neoplasms
protein synthesis
chemical derivatives
Cells
Derivatives
prolylglycine
Proteins
Bearings (structural)
Pyrrolidonecarboxylic Acid
drug delivery systems
oximes
molecular chaperones
neoplasms
Molecular Chaperones
Oximes
antineoplastic agents

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate. / Schreier, Verena Natalie; Petho, Lilla; Orbán, Erika; Marquardt, Andreas; Petre, Brindusa Alina; Mező, G.; Manea, Marilena.

In: PLoS One, Vol. 9, No. 4, e94041, 09.04.2014.

Research output: Contribution to journalArticle

Schreier, Verena Natalie ; Petho, Lilla ; Orbán, Erika ; Marquardt, Andreas ; Petre, Brindusa Alina ; Mező, G. ; Manea, Marilena. / Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate. In: PLoS One. 2014 ; Vol. 9, No. 4.
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