SenolyticsFisetin blocks sumoylation of tumor suppressor p53 and promote its activity

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Fisetin blocks sumoylation of tumor suppressor p53 and promote its activity

Post by AlbertY » Sat Jun 13, 2020 3:55 pm

This paper provides the mechanism of anti-cancer property of fisetin.
Fisetin was previously reported to induce the p53-mediated apoptotic pathway in human renal carcinoma cells [40]. Yet, the underlying mechanism and direct connection to SUMO1 has not been described to date. Numerous studies indicate that sumoylation is elevated in tumor cells in comparison to normal cells [41]. In colon cancer patients, it was shown that the combined elevated expression of SUMO1 and p53 leads to increased metastasis, and moreover, p53 is predominantly sumoylated in colon cancer cell lines [34]. Fisetin has also been shown to exert its anti-cancer effect by inducing cell cycle arrest and apoptosis in bladder cancer cells through activation of p53 [42]. Our study demonstrates that fisetin treatment inhibits p53 sumoylation, suggesting a molecular mechanism underlying fisetin action. It was previously shown that p53 sumoylation promotes nuclear export and thus inactivation of p53-mediated apoptosis [43]. Overall, our findings suggest a potential use for fisetin and its mimetics as novel p53 sumoylation inhibitors in cancer treatment.

Ph.D. student at Harvard Medical School, doing research on aging