Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
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

e0312572

Informations 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.

Auteurs

Osama A Mohammed (OA)

Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Mahmoud E Youssef (ME)

Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.

Rabab S Hamad (RS)

Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, Saudi Arabia.
Central Laboratory, Theodor Bilharz Research Institute, Giza, Egypt.

Mustafa Ahmed Abdel-Reheim (MA)

Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt.

Lobna A Saleh (LA)

Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, Saudi Arabia.

Mohannad Mohammad S Alamri (MMS)

Department of Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Muffarah Hamid Alharthi (MH)

Department of Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Jaber Alfaifi (J)

Department of Child Health, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Masoud I E Adam (MIE)

Department of Medical Education and Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Ali M S Eleragi (AMS)

Department of Microorganisms and Clinical Parasitology, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Ahmed Senbel (A)

Department of Surgical Oncology, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Alshaimaa A Farrag (AA)

Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Assad Ali Rezigalla (AA)

Department of Anatomy, College of Medicine, University of Bisha, Bisha, Saudi Arabia.

Hend S El-Wakeel (HS)

Physiology Department, Benha Faculty of Medicine, Benha University, Qalubyia, Egypt.
Physiology Department, Al-Baha Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia.

Mohammed A Attia (MA)

Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.

Hussein M El-Husseiny (HM)

Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Benha, Egypt.

Tohada M Al-Noshokaty (TM)

Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt.

Ahmed S Doghish (AS)

Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo, Cairo, Egypt.
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

Ahmed Gaafar Ahmed Gaafar (AGA)

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, Egypt.

Sameh Saber (S)

Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.

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Classifications MeSH