What type of study is this?

This is a In Vitro Study study.

March 15, 2026Open Access

Deciphering the therapeutic potential of 3,4-Dihydrocoumarin in cervical cancer: A combined network pharmacology and in vitro study

Key Points

This research evaluates the therapeutic potential of 3,4-Dihydrocoumarin against cervical cancer.
Network pharmacology analysis was conducted to identify major targets.
In vitro assays were performed on cervical cancer cell lines HeLa and SiHa.
Pharmacokinetics and safety were assessed using SwissADME and ProTox-III.
Protein-ligand interactions were explored via docking and molecular dynamics simulations.
3,4-Dihydrocoumarin significantly suppressed cell proliferation and induced apoptosis.
The compound caused mitochondrial dysfunction leading to ATP loss and reduced ROS levels.
Pharmacokinetic studies suggested favorable safety and drug-like properties.

Abstract

• 3,4-DHC from Curcuma caesia shows favorable ADME and safety profile. • Network pharmacology identified CDK2, MMP9, and AKT1 as hub targets. • Docking and MD simulations confirmed strong protein–ligand interactions. • 3,4-DHC suppressed proliferation and triggered apoptosis in cervical cells. • Induced mitochondrial dysfunction with ATP loss and ROS suppression. Coumarin derivatives represent a versatile scaffold for anticancer drug discovery. This study explored the therapeutic potential of 3,4-dihydrocoumarin (3,4-DHC), a major bioactive non-curcuminoid metabolite from Curcuma caesia , against cervical carcinoma. Phytocomponents were characterized by LC-HRMS while pharmacokinetics and safety were assessed using SwissADME, Deep-pk, and ProTox-III. Network pharmacology integrating SwissTarget, GeneCards, and DisGeNET identified candidate targets followed by functional enrichment (DAVID) and hub gene prioritization (CytoNCA). Protein-ligand interactions were probed by AutoDock Vina and validated through 500 ns GROMACS simulations. Expression profiles were examined via GEPIA2 and Human Protein Atlas. In vitro validation employed HeLa and SiHa cells using MTT, Annexin V/PI, mitochondrial potential and ROS assays, ATP determination, and western blot analysis. 3,4-DHC displayed favorable oral bioavailability, low toxicity, and drug-likeness. Network analysis highlighted CDK2, MMP9, and AKT1 as critical nodes among the hub genes. Docking predicted strong binding (−7.2 to −8.4 kcal/mol), corroborated by stable and energetically favorable MD interactions. Transcriptomic datasets confirmed overexpression and modulated promoter methylation of these targets in cervical tumors. Functionally, 3,4-DHC inhibited proliferation, induced apoptosis, disrupted mitochondrial homeostasis, reduced ATP levels, and suppressed ROS, indicating impaired bioenergetics. 3,4-DHC exerts antitumor activity by targeting oncogenic regulators and triggering mitochondrial dysfunction, but the high concentration range needs to be addressed. These findings suggest 3,4-DHC as a potential anticancer molecule.

Deciphering the therapeutic potential of 3,4-Dihydrocoumarin in cervical cancer: A combined network pharmacology and in vitro study

Key Points

Abstract

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