Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.
Vinca Alkaloids
/ pharmacology
Animals
Carcinoma, Hepatocellular
/ drug therapy
Rats
Liver Neoplasms
/ drug therapy
Male
Diethylnitrosamine
/ toxicity
Apoptosis
/ drug effects
Humans
Nootropic Agents
/ pharmacology
Cell Proliferation
/ drug effects
STAT3 Transcription Factor
/ metabolism
NF-kappa B
/ metabolism
Cyclin D1
/ metabolism
Oxidative Stress
/ drug effects
Liver
/ drug effects
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Intercellular Adhesion Molecule-1
/ metabolism
Hep G2 Cells
Transforming Growth Factor beta1
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2024
2024
Historique:
received:
24
05
2024
accepted:
04
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.
Identifiants
pubmed: 39480853
doi: 10.1371/journal.pone.0312572
pii: PONE-D-24-18529
doi:
Substances chimiques
vinpocetine
543512OBTC
Vinca Alkaloids
0
Diethylnitrosamine
3IQ78TTX1A
Nootropic Agents
0
STAT3 Transcription Factor
0
NF-kappa B
0
Cyclin D1
136601-57-5
Ccnd1 protein, rat
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Stat3 protein, rat
0
Intercellular Adhesion Molecule-1
126547-89-5
Hif1a protein, rat
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0312572Informations de copyright
Copyright: © 2024 Mohammed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.