Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

Paper

Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

Published 1990 · G. Pogány, A. Jeney, J. Tímár

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Abstract

The mechanism of action of 5-hexyl-2-'deoxyuridine (HUdR), a compound with antitumor activity, has been investigated in the HM cell lines derived from the highly metastatic variant of Lewis lung carcinoma (3LL-HH). It was shown that this pyrimidine analog did not inhibit the biosynthesis of nucleotides but modified the biosynthesis of glycoconjugates. The incorporation of [14C]-glucosamine into cytoplasmic glycoconjugates [glycosaminoglycan (GAG), glycolipid (GL), glycoprotein (GP), neutral polysaccharide (NP)] decreased to a similar level. The [14C]-glucosamine derived radioactivity was reduced to about 60-70% of the untreated controls in the presence of 15 micrograms/ml HUdR, which caused no inhibition of cell proliferation. These results might be explained by the reduced conversion of glucosamine into uridine-5'-diphospho-hexosamine. As more reduction was observed in the glucosamine labeling of glycoconjugates in nuclei and extracellular compartment, it may be conceivable that the intracellular transport of certain glycoconjugates (GAG, GP) is also affected by HUdR. In the extracellular compartment the reduced level of GAG labeling was the most apparent change. However, at a higher concentration of HUdR (75 micrograms/ml) there was a higher radioactivity in the combined GL + GP fraction. Using [35S]-labeling, the GAG fractions also showed a decreased radioactivity but only at the concentration of 75 micrograms/ml HUdR.

In Vitro Study

Study Snapshot

5-hexyl-2'-deoxyuridine (HUdR) reduces glycoconjugate biosynthesis in highly metastatic Lewis lung carcinoma cells without inhibiting cell proliferation, potentially affecting intracellular transport of certain glycoconjugates.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

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References

Citations

UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology

UGDH is a potential prognostication marker in oncology and a therapeutic target in cancer biology, involved in key cancer signaling pathways.

Extracellular matrix as target for antitumor therapy

Selective inhibitors of ECM components, such as heparanase and v5 integrin, show promise in controlling tumor progression and metastasis driven by ECM-mediated signaling.

Modulation of heparan‐sulphate/chondroitin‐sulphate ratio by glycosaminoglycan biosynthesis inhibitors affects liver metastatic potential of tumor cells

Anti-HS agents could potentially be anti-metastatic, as tumor cells with a high heparan sulphate/chondroitin sulphate ratio are more likely to form liver metastases.

Relationships between the chromatographic retention data and the effects of nucleoside derivatives in highly metastatic 3LL cells.

Nucleoside derivatives' effects on cellular uptake and DNA incorporation in highly metastatic 3LL cells are influenced by their specific hydrophobic and adsorption surface areas.

Modulation of membrane phenotype, matrix adhesion and microinvasiveness of metastatic tumour cells by HUdR

HUdR may be a promising anti-metastatic agent by modifying metastatic tumor cells' membrane phenotype, matrix adhesion, and microinvasiveness, without affecting cell proliferation.