Related Experiment Video
Updated: Jun 18, 2025
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug
Jack Porter1, Amanda R Noble2, Nathalie Signoret2
1Centre for Glycoscience and School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom.
Abstract:
Nucleoside analogues are established treatments for cancer and viral infection. Gemcitabine is a commonly employed nucleoside analogue displaying anticancer properties against a range of tumor types but is rapidly inactivated in vivo. Efforts to bolster its pharmaceutical profile include investigating prodrug forms. Herein, we explore the synthesis of a novel glucose-gemcitabine glycoconjugate, targeting uptake via glucose transport. We select a redox-reactive disulfide linker for conjugation of gemcitabine (through N4-cytosine) with glucose. Evaluation of this glycoconjugate reveals increased toxicity against androgen insensitive PC3 prostate cancer cells compared to LNCaP (which have lower levels of glucose transporter GLUT1). These preliminary results suggest that glycoconjugation of nucleosides may be an effective approach to targeting cells which display increased uptake and metabolism of glucose.
Insights
Researchers developed a novel glucose-gemcitabine glycoconjugate to improve cancer treatment. This prodrug demonstrated enhanced toxicity against prostate cancer cells with high glucose transporter levels, suggesting a targeted therapy approach.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Drug Delivery
Background:
- Nucleoside analogues like gemcitabine are vital in treating cancer and viral infections.
- Gemcitabine's rapid inactivation in vivo necessitates strategies to improve its pharmaceutical profile, such as prodrug development.
Purpose of the Study:
- To synthesize and evaluate a novel glucose-gemcitabine glycoconjugate.
- To target cancer cells by exploiting glucose transport mechanisms.
- To assess the efficacy of a redox-reactive disulfide linker in this conjugation.
Main Methods:
- Synthesis of a glucose-gemcitabine glycoconjugate using a redox-reactive disulfide linker.
- Conjugation of gemcitabine (via N4-cytosine) to glucose.
- Evaluation of the glycoconjugate's toxicity against prostate cancer cell lines (PC3 and LNCaP).
Main Results:
- The novel glucose-gemcitabine glycoconjugate exhibited increased toxicity against androgen-insensitive PC3 prostate cancer cells.
- PC3 cells, which have higher levels of glucose transporter GLUT1, were more sensitive than LNCaP cells.
- This suggests that targeting glucose transporters can enhance the efficacy of nucleoside analogues.
Conclusions:
- Glycoconjugation of nucleosides represents a promising strategy for developing targeted cancer therapies.
- This approach may be particularly effective for cancers with increased glucose uptake and metabolism.
- Further research into glucose-targeted nucleoside prodrugs could lead to improved treatment outcomes.
More Related Videos
13:21Chemically-blocked Antibody Microarray for Multiplexed High-throughput Profiling of Specific Protein Glycosylation in Complex Samples
Published on: May 4, 2012
08:17A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
Published on: April 16, 2021
