These data support the potential of B. serrata-derived compounds as novel anti-hepatocarcinoma agents.

Cytotoxic Activity ofRoxb. Essential Oil and Acetyl-11-Keto-β-Boswellic Acid (AKBA) on Hepatocellular Carcinoma Cells: In Vitro and In Silico Study.

Francisco Javier Alarcon-Aguilar, Diana Laura Torres-Chacón, Alfredo Suárez-Alonso, Samuel Enoch Estrada-Soto, Luis Enrique Gómez-Quiroz, JoséLuís Eduardo Flores Sáenz, Elisa VegaÁvila, Gerardo Blancas Flores, Abraham Giacoman Martínez, Beatriz Mora Ramiro, Julio César Almanza-Pérez

Int J Mol Sci

Jul 2, 2026

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Abstract

Hepatocellular carcinoma is one of the most aggressive malignancies worldwide, with limited therapeutic options.Roxb., an Indian medicinal tree, produces a resin rich in essential oil and boswellic acids, particularly acetyl-11-keto-β-boswellic acid (AKBA), with demonstrated antiproliferative and pro-apoptotic activities. This study investigated the cytotoxic effects ofessential oil and AKBA on hepatocarcinoma Huh-7 cells in both monolayer and three-dimensional spheroid cultures and characterized the underlying molecular targets. Essential oil was extracted and analyzed by gas chromatography-mass spectrometry (GC-MS). Cytotoxicity was assessed using the cell counting kit-8 (CCK-8). Three-dimensional spheroid cultures were also established to evaluate anti-tumoral potential. Expression of cyclin D1, cyclin-dependent of kinase 4 (CDK4) (cyclin-dependent kinase inhibitor 1A (p21), E-cadherin, (alpha fetoprotein) AFP, epithelial cell adhesion molecule (EpCAM), Myeloid cell leukemia-1 (Mcl-1), and caspase-3 was analyzed by western blot. In addition, an in silico analysis was performed on the main constituents ofessential oil targeting 5-lipoxygenase (5LO). The results showed cytotoxic effects, with AKBA exhibiting greater potency than the essential oil. Cytotoxicity was associated with caspase-3-mediated apoptosis, with minimal effects on cell cycle and epithelial-mesenchymal transition markers. The in silico analysis predicted that some compounds may act as competitive inhibitors of the 5LO at the catalytic site and partially activate pro-apoptotic pathways. These data support the potential of-derived compounds as novel anti-hepatocarcinoma agents, with AKBA and longifolene as leads for further preclinical and clinical research.