Fig. 4

Capsaicin induces simultaneous autophagic degradation of mutant p53 and reactivation of wild-type p53. Capsaicin activates TRPV1, leading to double-strand DNA breaks and phosphorylation of histone H2AX. ATM kinase phosphorylates and activates a number of DNA repair and checkpoint proteins, including p53, Brca1, and Chk2, ultimately causing cell cycle arrest. On the other hand, capsaicin induces autophagic degradation of p53R175H and p53R273H and reactivates intact p53 that does not harbor mutations in the DNA-binding domain. Thus, expression of apoptotic genes such as Puma, Bax, and DRAM increases