Cyclin-dependent kinase 1 as a potential target for lycorine against hepatocellular carcinoma.
Amaryllidaceae Alkaloids
/ chemistry
Animals
Antineoplastic Agents
/ pharmacology
CDC2 Protein Kinase
/ antagonists & inhibitors
Carcinoma, Hepatocellular
/ drug therapy
Cell Line, Tumor
Cellular Senescence
Cyclin B1
/ genetics
Cyclin B2
/ genetics
Drug Delivery Systems
Gene Expression Regulation, Enzymologic
/ drug effects
Humans
Liver Neoplasms
/ drug therapy
Male
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Molecular Structure
Phenanthridines
/ chemistry
Xenograft Model Antitumor Assays
CDK1
Cancer
Cell senescence
HCC
Lycorine
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
08
07
2021
revised:
03
10
2021
accepted:
04
10
2021
pubmed:
22
10
2021
medline:
7
1
2022
entrez:
21
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34673013
pii: S0006-2952(21)00422-6
doi: 10.1016/j.bcp.2021.114806
pii:
doi:
Substances chimiques
Amaryllidaceae Alkaloids
0
Antineoplastic Agents
0
CCNB1 protein, human
0
CCNB2 protein, human
0
Cyclin B1
0
Cyclin B2
0
Phenanthridines
0
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
lycorine
I9Q105R5BU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114806Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.