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

Abstract

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
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References

  • References29
  • Citations2

Citations

Mentioned in this Paper

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

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