Curcumin has shown promise as a safe and specific
anticancer agent. The
COP9 signalosome (CSN) component CSN5, a known specific target for
curcumin, can control p53 stability by increasing its degradation through
ubiquitin system. But the correlation of CSN5-controlled p53 to anticancer
therapeutic effect of
curcumin is currently unknown. Here we showed that CSN5-controlled p53 was transcriptional inactive and responsible for autophagy in human normal BJ cells and
cancer HepG2 cells under
curcumin treatment. Of note, CSN5-initiated cellular autophagy by
curcumin treatment was abolished in p53-null HCT116p53-/-
cancer cells, which could be rescued by reconstitution with wild-type p53 or transcription inactive p53 mutant p53R273H. Furthermore, CSN5-controlled p53 conferred a pro-survival autophagy in diverse
cancer cells response to
curcumin. Genetic p53 deletion, as well as autophagy pharmacological inhibition by
chloroquine, significantly enhanced the
therapeutic effect of
curcumin on
cancer cells in vitro and in vivo, but not normal cells. This study identifies a novel CSN5-controlled p53 in autophagy of human cells. The p53 expression state is a useful
biomarker for predicting the anticancer
therapeutic effect of
curcumin. Therefore, the pharmacologic autophagy manipulation may benefit the ongoing anticancer clinical trials of
curcumin.