Bee venom exhibits anti-cancer effects on tongue carcinoma cells by arresting cell cycle, inducing apoptosis, and suppressing cell migration

Enas Sabry; Hagar M Zayed; Ola M Ezzatt; Iman Fathy; Hebatt-Allah S Elsayeh; Nashwa El-Khazragy; Suzan SeifAllah Ibrahim

doi:10.1590/1678-7757-2025-0188

Authors

Enas Sabry Ain Shams University, Faculty of Dentistry, Department of Oral Medicine, Periodontology and Oral Diagnosis, Cairo https://orcid.org/0000-0002-3707-9600
Hagar M Zayed Ain Shams University, Faculty of Dentistry, Department of Oral Medicine, Periodontology and Oral Diagnosis, Cairo https://orcid.org/0000-0002-4344-8249
Ola M Ezzatt Ain Shams University, Faculty of Dentistry, Department of Oral Medicine, Periodontology and Oral Diagnosis, Cairo https://orcid.org/0000-0003-1656-5076
Iman Fathy Ain Shams University, Faculty of Dentistry, Central Lab of Stem Cells and Biomaterial Applied Research (CLSBAR), Cairo https://orcid.org/0000-0002-5219-2740
Hebatt-Allah S Elsayeh Beekeeping Research Department, Plant Protection Research Institute, Agricultural Research Center, Ministry of Agriculture, Giza https://orcid.org/0009-0002-8772-9453
Nashwa El-Khazragy Ain Shams University, Faculty of Medicine, Department of Clinical Pathology/Hematology, Cairo https://orcid.org/0000-0001-6646-4674
Suzan SeifAllah Ibrahim Ain Shams University, Faculty of Dentistry, Department of Oral Medicine, Periodontology and Oral Diagnosis, Cairo https://orcid.org/0000-0002-2335-6507

DOI:

https://doi.org/10.1590/1678-7757-2025-0188

Keywords:

Apitoxin, Apis mellifera, Cancer therapy, Honeybee

Abstract

Objective Tongue squamous cell carcinoma (TSCC) is an aggressive oral cancer with notable treatment resistance. This in vitro study investigated anti-cancer effects of honey bee venom (BV)—a mixture of bioactive compounds—on the human TSCC cell line. Methodology The cytotoxicity of serial BV concentrations (0.01–100 µg/mL) was tested on the cultured human TSCC cell line (HNO-97) to determine the half-maximal inhibitory concentration (IC₅₀) value. Group I (BV) included cells treated with IC₅₀ of BV, and Group II (control) received no treatment; both were incubated for 48 hours. The apoptotic effect of BV was evaluated using the Annexin V assay and the BAX and BCL-2 gene expression. The BV effect on cell viability, proliferation, and division was evaluated by cell cycle assay. Additionally, Transwell migration assays were performed to demonstrate the potential impact of BV on cell migration. Results BV showed dose-dependent cytotoxicity and anti-proliferative activity on HNO-97 cells (IC₅₀: 12.96 μg/mL). The treated group exhibited cell cycle arrest, reduced cell migration, significantly decreased BCL-2 gene expression (p=0.001), and increased BAX gene expression (p=0.03) compared to the untreated group. Conclusion BV demonstrated anti-cancer activity on human TSCC by inducing apoptosis and inhibiting cell migration. These findings warrant further preclinical investigations to evaluate BV as an alternative for current tongue carcinoma therapies.

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Bee venom exhibits anti-cancer effects on tongue carcinoma cells by arresting cell cycle, inducing apoptosis, and suppressing cell migration

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