Aug 4, 2009

Galactosyl derivative of N(omega)-nitro-L-arginine: study of antiproliferative activity on human thyroid follicular carcinoma cells

Journal of Cellular Physiology
Daniela MelisiMaria Grazia Rimoli


The methyl ester prodrug of N(omega)-nitro-L-arginine (L-NAME) has been reported to exert anticancer effects against several human tumors, including thyroid carcinoma, by inhibiting nitric oxide synthase (NOS). However, chronic administration of L-NAME has often led to adverse events causing cardiovascular alterations due to its potential toxic effect. Here we report for the first time the synthesis of the galactosyl ester prodrug of N(omega)-nitro-L-arginine, NAGAL, a prodrug capable of inhibiting NOS more efficiently and with fewer adverse events than its parent drug. For this purpose RO82-W-1, a thyroid cell line derived from human follicular carcinoma, was used. MTT test results showed that NAGAL affected cell viability to a significantly greater extent than did L-NAME. Moreover, fluorescence activated cell sorter (FACS) analyses revealed that NAGAL, compared to L-NAME, was able to reduce nitric oxide (NO) production as well as increase the percentage of apoptotic thyreocytes. Western blot further confirmed the reduction in NOS-II expression by NAGAL. Finally, by using the LC-MS technique, we found that NAGAL elicited a higher increase in N(omega)-nitro-L-arginine (NA) concentration than did L-NAME. Thus, this study suggest...Continue Reading

  • References29
  • Citations2


  • References29
  • Citations2


Mentioned in this Paper

Flow Cytometry
Apoptosis, Intrinsic Pathway
Western Blotting
Fluorescence-Activated Cell Sorting
Nitric Oxide Synthase Type II
Thyroid Diseases
Cell Proliferation

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Head And Neck Squamous Cell Carcinoma

Squamous cell carcinomas account for >90% of all tumors in the head and neck region. Head and neck squamous cell carcinoma incidence has increased dramatically recently with little improvement in patient outcomes. Here is the latest research on this aggressive malignancy.

Signaling in Adult Neurogenesis

Neural stem cells play a critical role in the production of neuronal cells in neurogenesis is of great importance. Of interest is the role signalling mechanisms in adult neurogenesis. Discover the latest research on signalling in adult neurogenesis.

Psychiatric Chronotherapy

Psychiatric Chronotherapy considers the circadian rhythm as a major factor for optimizing therapeutic efficacy of psychiatric interventions. Discover the latest research on Psychiatric Chronotherapy here.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.