A mutated p53 status did not prevent the induction of apoptosis by sulforaphane, a promising anti-cancer drug.
We investigated apoptosis induction by sulforaphane on three cell lines characterized by a different p53 status. In particular, we used p53-knock-out fibroblasts from newborn mice transfected with the p53-Ser220 mutation, observed in Li-Fraumeni Syndrome patients, as a model of mutated p53 status. Moreover, immortalized fibroblasts from newborn mice expressing or lacking p53 (p53 +/+ and p53-/-, respectively) have been used to verify whether mutated p53 status could prevent sulforaphane-induced apoptotic events. Sulforaphane was able to induce apoptosis on all three cell lines. Indeed, the caspase-3 assays and poly(ADP-ribose)polymerase (PARP) cleavage data indicated that sulforaphane stimulated caspase-3-like activity and degradation of PARP. However, cells with a wild-type or mutated p53 appeared to be more sensitive to the effects of sulforaphane than cells lacking p53. Taken together, our results suggest that sulforaphane could act by a p53-independent pathway. For this reason, sulforaphane can be viewed as a novel agent useful not only in the treatment of Li-Fraumeni-associated tumors but also drug resistant tumors where p53 dysregulation is a feature.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, via Irnerio 48, 40126, Bologna, Italy. carmela.fimognari@unibo.it
Sangiorgi
Luca
L
Capponcelli
Silvia
S
Nüsse
Michael
M
Fontanesi
Silvia
S
Berti
Fausto
F
Soddu
Silvia
S
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016158:Genes, p53; D017879:Isothiocyanates; D051379:Mice; D009154:Mutation; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C016766:sulforaphane