Modulation of glutathione transferase P1-1 activity by retinoic acid in neuroblastoma cells.
The ability of retinoic acid to modulate glutathione S-transferase P1-1 (GSTP1-1) activity has important implications both for cancer prevention and for anticancer therapy. We investigated GSTP1-1 expression and activity in the human neuroblastoma cell line SK-N-BE(2) (genotype A*/B*) under basal conditions and during 48-h incubation with 0.1 microM all-trans-retinoic acid. The steady-state levels of glutathione transferase P1-1 mRNA and protein during 48-h incubation with all-trans-retinoic acid did not increase substantially, but we detected a significant reduction of GSTP1-1 specific activity. This reduction in enzymatic activity could not be ascribed to a differential action of retinoic acid on the gene variants A* and B*; indeed, the two GSTP1-1 isoforms have different affinities toward 1-chloro-2,4-dinitrobenzene (CDNB), while we found a substantial invariance of the K(m) (CDNB) in the cytosol during retinoid treatment. A modulatory effect of retinoic acid on other enzymes involved in glutathione transferase P1-1 metabolism, such as the retinoic acid-induced tissue trans-glutaminase, might be hypothesized, as well as a direct inactivation of GSTP1-1 by the oxidative stress that characterizes the early phases of apoptosis.
Bernardini
S
S
Department of Internal Medicine, University of Tor Vergata, Rome, Italy. bernardini@med.uniroma2.it
Melino
G
G
Cortese
C
C
Ballerini
S
S
Annicchiarico-Petruzzelli
M
M
Bernassola
F
F
Corazzari
M
M
Federici
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014212:Tretinoin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase