Molecule Information

General Information of the Molecule (ID: Mol04265)

• Name: Threonine 34 phosphorylation (Thr34) ,Homo sapiens
• Synonyms: Threonine 34 phosphorylation (Thr34)
• Molecule Type: Protein

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

Isoliquiritigenin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [1]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Isoliquiritigenin
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Akt-Wee1-CDK1 signaling pathway; Regulation; N.A.
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC-4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: CCD-118Sk cells; N.A.; Homo sapiens (Human); CVCL_Y116
• In Vivo Model: Athymic female nude mice; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay; Ubiquitination assay; Akt kinase activity assay; Immunohistochemistry
• Experiment for Drug Resistance: MTS assay; Soft agar assay; Plate colony formation assay; In vivo tumor growth assay; Blood assay
• Mechanism Description: 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.

References

• Ref 1: Isoliquiritigenin Inhibits Oral Squamous Cell Carcinoma and Overcomes Chemoresistance by Destruction of Survivin. Am J Chin Med. 2023;51(8):2221-2241.