Butein inhibits cancer cell growth by rescuing the wild-type thermal stability of mutant p53.

p53 is a transcription factor that activates the expression of various genes involved in the maintenance of genomic stability, and more than 50% of cancers harbor inactivating p53 mutations, which are indicative of highly aggressive cancer and poor prognosis. Pharmacological targeting of mutant p53 to restore the wild-type p53 tumor-suppressing function is a promising strategy for cancer therapy. In this study, we identified a small molecule, Butein, that reactivates mutant p53 activity in tumor cells harboring the R175H or R273H mutation.

Buxus alkaloid compound destabilizes mutant p53 through inhibition of the HSF1 chaperone axis.

Background: P53 is the most frequently mutated gene in most tumour types, and the mutant p53 protein accumulates at high levels in tumours to promote tumour development and progression. Thus, targeting mutant p53 for degradation is one of the therapeutic strategies used to manage tumours that depend on mutant p53 for survival. Buxus alkaloids are traditionally used in the treatment of cardiovascular diseases.