Protein Expression Profile of HT-29 Human Colon Cancer Cells After Treatment with a Cytotoxic Daunorubicin-GnRH-III Derivative Bioconjugate

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Apr 11

PMID 24718594

Citations 3

Authors

Verena Natalie Schreier

Lilla Petho

Erika Orban

Andreas Marquardt

Brindusa Alina Petre

Gabor Mezo

Marilena Manea

Affiliations

Soon will be listed here.

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(Da = 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.

Citing Articles

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Petho L, Mezo G, Schlosser G Molecules. 2019; 24(16).

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