RESUMO
The increased stability of mutant p53 (Mutp53) plays a crucial role in its gain of function, making proteins involved in its stabilization promising targets for drug intervention. Although curcumin is known to exhibit anti-cancer effects, its role as a deubiquitinase (DUB) inhibitor in Mutp53 destabilization remains poorly explored. Our study demonstrates that curcumin treatment induced ubiquitination and destabilization of Mutp53 but not Wild-type p53 (WTp53) in cancer cells. Furthermore, proteasome and lysosome inhibitors failed to reverse the effect of curcumin, indicating Mutp53 destabilization is possibly via an alternate mechanism. Intriguingly, curcumin treatment also resulted in the nuclear aggregation of the Mutp53 protein, which was rescued by combined Dithiothreitol (DTT) treatment. Similar to curcumin, a broad-spectrum deubiquitinase inhibitor induced Mutp53 aggregation implying curcumin possibly acts by inhibiting deubiquitinases. Additionally, curcumin treatment inhibited colony-forming abilities, induced cytoplasmic vacuolation, and cell death selectively in Mutp53-expressing cells. Collectively, our study highlights the potential of curcumin as a promising therapeutic agent for targeting Mutp53-expressing cancer cells.
