Isoliquiritigenin Inhibits Oral Squamous Cell Carcinoma and Overcomes Chemoresistance by Destruction of Survivin

Am J Chin Med. 2023 Nov 4:1-21. doi: 10.1142/S0192415X23500957. Online ahead of print.ABSTRACTThe oncoprotein survivin plays a pivotal role in controlling cell division and preventing apoptosis by inhibiting caspase activation. Its significant contribution to tumorigenesis and therapeutic resistance has been well established. Isoliquiritigenin (ISL), a natural compound, has been recognized for its powerful inhibitory effects against various tumors. However, whether ISL exerts regulatory effects on survivin and its underlying mechanism in oral squamous cell carcinoma (OSCC) remains unclear. Here, we found that ISL inhibited the viability and colony formation of OSCC, and promoted their apoptosis. The immunoblotting data showed that ISL treatment significantly decreased survivin expression. Mechanistically, ISL suppressed survivin phosphorylation on Thr34 by deregulating Akt-Wee1-CDK1 signaling, which facilitated survivin for ubiquitination degradation. ISL inhibited CAL27 tumor growth and decreased p-Akt and survivin expression in vivo. Meanwhile, survivin overexpression caused cisplatin resistance of OSCC cells. ISL alone or combined with cisplatin overcame chemoresistance in OSCC cells. Overall, our results revealed that ISL exerted potent inhibitory effects via inducing Akt-dependent survivin ubiquitination in OSCC cells.PMID:37930332 | DOI:10.1142/S0192415X23500957
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Source Type: research