Jump to main content
Jump to site search


Development of potent CPP6–gemcitabine conjugates against human prostate cancer cell line (PC-3)

Author affiliations

Abstract

Gemcitabine (dFdC) is a nucleoside analogue used in the treatment of various cancers, being a standard treatment for advanced pancreatic cancer. The effect of gemcitabine is severely compromised due to its rapid plasma degradation, systemic toxicity and drug resistance, which restricts its therapeutic efficacy. Our main goal was to develop new active conjugates of dFdC with novel cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug. All new peptides were prepared by solid phase peptide synthesis (SPPS), purified and characterized by HPLC and LC-MS. Cell-penetrating peptides (CPP) contain a considerably high ratio of positively charged amino acids, imparting them with cationic character. Tumor cells are characterized by an increased anionic nature of their membrane surface, a property that could be used by CPP to target these cells. The BxPC-3, MCF-7 and PC-3 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that conjugating dFdC with CPP6 significantly enhanced cell growth inhibitory activity on PC-3 cells, with IC50 between 14 and 15 nM. These new conjugates have potential to become new therapeutic tools for cancer therapy.

Graphical abstract: Development of potent CPP6–gemcitabine conjugates against human prostate cancer cell line (PC-3)

Back to tab navigation

Supplementary files

Article information


Submitted
18 Oct 2019
Accepted
31 Dec 2019
First published
10 Jan 2020

RSC Med. Chem., 2020, Advance Article
Article type
Research Article

Development of potent CPP6–gemcitabine conjugates against human prostate cancer cell line (PC-3)

C. Correia, C. P. R. Xavier, D. Duarte, A. Ferreira, S. Moreira, M. H. Vasconcelos and N. Vale, RSC Med. Chem., 2020, Advance Article , DOI: 10.1039/C9MD00489K

Social activity

Search articles by author

Spotlight

Advertisements