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Cyclin-dependent kinase 1 as a potential target for lycorine against hepatocellular carcinoma.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2021 Nov; Vol. 193, pp. 114806. Date of Electronic Publication: 2021 Oct 18. - Publication Year :
- 2021
-
Abstract
- The pathological changes and possible underlying molecular mechanisms of hepatocellular carcinoma (HCC) are currently unclear. Effective treatment of this pathological state remains a challenge. The purpose of this study is to obtain some key genes with diagnostic and prognostic meaning and to identify potential therapeutic agents for HCC treatment. Here, CDK1, CCNB1 and CCNB2 were found to be highly expressed in HCC patients and accompanied by poor prognosis, and knockdown of them by siRNA drastically induced autophagy and senescence in hepatoma cells. Simultaneously, the anti-HCC effect of lycorine was comparable to that of interfering with these three genes, and lycorine significantly promoted the decrease both in protein and mRNA expression of CDK1. Molecular validation mechanistically demonstrated that lycorine might attenuate the degradation rate of CDK1 via interaction with it, which had been confirmed by cellular thermal shift assay and drug affinity responsive targets stability assay. Taken together, these findings suggested that CDK1, CCNB1 and CCNB2 could be regarded as potential diagnostic and prognostic biomarkers for HCC, and CDK1 might serve as a promising therapeutic target for lycorine against HCC.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Amaryllidaceae Alkaloids chemistry
Amaryllidaceae Alkaloids therapeutic use
Animals
Antineoplastic Agents therapeutic use
CDC2 Protein Kinase genetics
CDC2 Protein Kinase metabolism
Cell Line, Tumor
Cellular Senescence
Cyclin B1 genetics
Cyclin B1 metabolism
Cyclin B2 genetics
Cyclin B2 metabolism
Gene Expression Regulation, Enzymologic drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Molecular Structure
Phenanthridines chemistry
Phenanthridines therapeutic use
Xenograft Model Antitumor Assays
Amaryllidaceae Alkaloids pharmacology
Antineoplastic Agents pharmacology
CDC2 Protein Kinase antagonists & inhibitors
Carcinoma, Hepatocellular drug therapy
Drug Delivery Systems
Liver Neoplasms drug therapy
Phenanthridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 193
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34673013
- Full Text :
- https://doi.org/10.1016/j.bcp.2021.114806