Evidence map›Paper›PMID 39471041›Full record

ArticleAsian Pacific journal of cancer prevention : APJCP2024

Anti-viral and Apoptotic Induction of m-TOR Inhibitor Drugs against Hepatitis C Virus Activity and Hepatocellular Carcinoma Cell Line: In vitro and in silico.

Dina Mofed, Wafaa Ahmed, Reham N Mohaseb, Mohamed Rahouma, Ahmed Hassan Ibrahim Faraag, Salwa Sabet

Abstract read
In one paragraph

Article in Asian Pacific journal of cancer prevention : APJCP, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Dina MofedZoology Graduate Program, Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt.
Wafaa AhmedBiochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Giza, 12613, Egypt.
Reham N MohasebBotany department, faculty of Science, Tanta University, Tanta 31527, Egypt.
Mohamed RahoumaDepartment of Surgical Oncology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
Ahmed Hassan Ibrahim FaraagDepartment of Botany and Microbiology, Faculty of Science, Helwan University, Cairo 11795, Egypt.
Salwa SabetDepartment of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study investigated the potential of m-TOR inhibitor drugs (sirolimus, everolimus, and tacrolimus) in combating both hepatocellular carcinoma (HCC) and hepatitis C virus (HCV) replication.

methodsAfter treating HepG2 and PBMCs with the mammalian target of Rapamycin (m-TOR) inhibitors drugs; sirolimus, everolimus, and tacrolimus at different concentrations (1, 5, and 10 µM/µl), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase, and glutathione reductase), Fas-ligand level, tumor necrosis factor-α (TNF-α) level, caspase-3, -8, and -9 activities, and cell cycle analysis were measured. quantitative Real-time PCR, colony forming assay, molecular docking studies after infection of PBMCs with 1 ml (1.5 × 106 HCV) serum then incubated with m-TOR inhibitor drugs at their respective IC50 concentrations.

resultsIn HepG2 cells, treatment with these inhibitors resulted in suppressed cell viability, increased dead cell accumulation, and enhanced apoptotic signaling through elevated Fas-ligand and caspase activities. Additionally, cell cycle analysis revealed arrest in G0/G1 and G2/M phases, further hindering HCC progression. Furthermore, m-TOR inhibitor drugs significantly reduced HCV viral load and colony formation in infected PBMCs. This antiviral effect was accompanied by decreased TNF-α activity, suggesting potential modulation of the inflammatory response associated with HCV infection. Molecular docking studies provided theoretical support for these findings, with Sovaldi demonstrating the highest binding affinity towards key HCV targets compared to other m-TOR inhibitors. This suggests its potential as a potent HCV inhibitor, while also highlighting the potential of exploring m-TOR inhibitors for future HCV treatment development.

conclusionOverall, this study provides encouraging evidence for the potential of m-TOR inhibitor drugs as promising therapeutic agents for both HCC and HCV, warranting further investigation and optimization for clinical applications.

Indexed as

Antiviral AgentsApoptosisCarcinoma, HepatocellularCell ProliferationHepacivirusLiver NeoplasmsTOR Serine-Threonine KinasesComputer SimulationEverolimusHepatitis CHep G2 CellsHumansMolecular Docking SimulationSirolimusVirus ReplicationAntiviral AgentsEverolimusMTOR protein, humanSirolimusTOR Serine-Threonine KinasesDocking &emspHCCHCVm-TOR inhibitors drugs

Identifiers

PMID39471041
PMCPMC11711332

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.