Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
Falcarindiol induces apoptosis, ROS accumulation, and cell cycle arrest via EGFR/mTOR pathway modulation: an integrated in silico and in vitro study in cervical cancer.
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Timalsina Ganesh, Parida Bishnu Prasad, Radhakrishnan Megha, Khoiyang Tuliam, Singh Sunita, Narayan Gopeshwar
Аннотация
BACKGROUND: Falcarindiol, a bioactive polyacetylene, has shown cytotoxic effects in several cancers including breast, colorectal, and oral squamous carcinoma, but its pharmacological actions in cervical cancer are not well defined.
OBJECTIVES: This study aims to integrate in silico approaches to define the multi-target pharmacological mechanisms of falcarindiol in cervical cancer, including ADMET profiling, network pharmacology, target prioritization, and molecular docking especially of EGFR/mTOR associated signaling pathways. Simultaneously, the study aims to experimentally verify the anticancer activity of falcarindiol in cervical cancer cells by examining its impacts on cell viability, apoptosis, mitochondrial dysfunction, reactive oxygen species generation, senescence induction, and cell cycle regulation.
METHODS: Pharmacokinetic and toxicity properties were evaluated using in silico ADMET profiling. Potential molecular targets and signaling pathways were identified from integrated databases, with hub genes prioritized by protein-protein interaction analysis. Protein-ligand binding was assessed through docking. Gene expression and prognostic significance were analyzed using public cancer datasets. Functional effects of falcarindiol were validated in HeLa and SiHa cervical cancer cells by MTT assay, Annexin V/PI, and AO/PI staining, mitotracker intensity, H2DCFDA fluorescence, β-galactosidase staining, and cell cycle analysis.
RESULTS: Falcarindiol demonstrated favorable ADMET properties and low predicted toxicity. Target prioritization identified EGFR, ERBB2, mTOR, MMP9, and CASP3 as central nodes, with strong interactions confirmed for EGFR and mTOR. Expression analyses revealed upregulation and hypomethylation of these genes in cervical cancer. Falcarindiol reduced viability (IC50 ~ 125-150µM), induced apoptosis, disrupted mitochondrial membrane potential, increased ROS production, and caused G0/G1 arrest in vitro. Senescence was also enhanced in treated cells.
CONCLUSION: Falcarindiol exerts multi-targeted pharmacological actions in cervical cancer by modulating EGFR/mTOR signaling and apoptotic pathways, supporting its potential as a therapeutic lead compound.
OBJECTIVES: This study aims to integrate in silico approaches to define the multi-target pharmacological mechanisms of falcarindiol in cervical cancer, including ADMET profiling, network pharmacology, target prioritization, and molecular docking especially of EGFR/mTOR associated signaling pathways. Simultaneously, the study aims to experimentally verify the anticancer activity of falcarindiol in cervical cancer cells by examining its impacts on cell viability, apoptosis, mitochondrial dysfunction, reactive oxygen species generation, senescence induction, and cell cycle regulation.
METHODS: Pharmacokinetic and toxicity properties were evaluated using in silico ADMET profiling. Potential molecular targets and signaling pathways were identified from integrated databases, with hub genes prioritized by protein-protein interaction analysis. Protein-ligand binding was assessed through docking. Gene expression and prognostic significance were analyzed using public cancer datasets. Functional effects of falcarindiol were validated in HeLa and SiHa cervical cancer cells by MTT assay, Annexin V/PI, and AO/PI staining, mitotracker intensity, H2DCFDA fluorescence, β-galactosidase staining, and cell cycle analysis.
RESULTS: Falcarindiol demonstrated favorable ADMET properties and low predicted toxicity. Target prioritization identified EGFR, ERBB2, mTOR, MMP9, and CASP3 as central nodes, with strong interactions confirmed for EGFR and mTOR. Expression analyses revealed upregulation and hypomethylation of these genes in cervical cancer. Falcarindiol reduced viability (IC50 ~ 125-150µM), induced apoptosis, disrupted mitochondrial membrane potential, increased ROS production, and caused G0/G1 arrest in vitro. Senescence was also enhanced in treated cells.
CONCLUSION: Falcarindiol exerts multi-targeted pharmacological actions in cervical cancer by modulating EGFR/mTOR signaling and apoptotic pathways, supporting its potential as a therapeutic lead compound.