Novel CDK9 inhibitor oroxylin A promotes wild-type P53 stability and prevents hepatocellular carcinoma progression by disrupting both MDM2 and SIRT1 signaling

• Published in: Acta pharmacologica Sinica Vol. 43; no. 4; pp. 1033 - 1045
• Main Authors: Yao, Jing-yue, Xu, Shu, Sun, Yue-ning, Xu, Ye, Guo, Qing-long, Wei, Li-bin
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.04.2022; Nature Publishing Group
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Carcinoma, Hepatocellular - pathology; Cyclin-dependent kinase; Cyclin-dependent kinase 9; Cyclin-Dependent Kinase 9 - metabolism; Cyclin-dependent kinases; Etiology; Flavonoids; Gene silencing; Hepatocellular carcinoma; Humans; Immunology; Internal Medicine; Kinases; Liver cancer; Liver Neoplasms - pathology; MDM2 protein; Medical Microbiology; Mice; p53 Protein; Pharmacology/Toxicology; Proto-Oncogene Proteins c-mdm2 - metabolism; SIRT1 protein; Sirtuin 1 - metabolism; Therapeutic targets; Toxicity; Tumor Suppressor Protein p53 - metabolism; Tumors; Ubiquitination; Vaccine; oroxylin A; Wt-p53 stabilization; hepatocellular carcinoma; inhibition of CDK9

Hepatocellular carcinoma (HCC) is one of the most lethal tumours worldwide. However, the effects of first-line sorafenib treatment in advanced HCC fail to prolong patients’ survival due to the highly heterogeneous characteristics of HCC etiology. Cyclin-dependent kinase 9 (CDK9) is an important targ...