U. Wellnitz et al., INACTIVATION OF RIBONUCLEOTIDE REDUCTASE IN TUMOR-CELLS AND INHIBITION OF TUMOR-CELL GROWTH BY P-ALKOXYPHENOLS, Melanoma research, 7(4), 1997, pp. 288-298
Citations number
36
Categorie Soggetti
Medicine, Research & Experimental",Oncology,"Dermatology & Venereal Diseases
A significant correlation between the inactivation of the growth-regul
ating enzyme ribonucleotide reductase (RR) with the growth inhibition
of four different tumour cell lines has been found for seven different
p-alkoxyphenol derivatives with varying lengths of alkyl side chain.
In Novikoff hepatoma and human leukaemia cells, inactivation of RR by
p-alkoxyphenols was monitored by electron paramagnetic resonance (EPR)
spectroscopy of the catalytically essential tyrosyl radical in the su
bunit R2 of RR. A significant inhibition of cellular growth of Novikof
f hepatoma cells, human leukaemia cells and two human melanoma cell li
nes (MeWo and M5) by p-alkoxyphenols was also observed by growth inhib
ition assays, Inactivation of RR in whole tumour cells as well as inhi
bition of cellular growth of tumour cell lines by p-alkoxyphenols both
show an increase in inhibition with increasing length of the alkyl si
de chain; the most effective inhibitors are p-isobutoxyphenol, p-butox
yphenol and p-propoxyphenol. The enzyme RR, and in particular the cata
lytically essential tyrosyl radical in the active site, is recognized
as an important cellular target for growth inhibition of Novikoff hepa
toma cells, human leukaemia cells and melanoma cells by p-alkoxyphenol
s. Thus, the most potent RR inhibitors p-isobutoxyphenol, p-butoxyphen
ol and p-propoxyphenol - may be considered as future antiproliferative
drugs for the systemic treatment of melanoma as well as leukaemia and
possibly other malignancies.