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

**Authors:** Enas SABRY, Hagar M ZAYED, Ola M EZZATT, Iman FATHY, Hebatt-Allah S ELSAYEH, Nashwa EL-KHAZRAGY, Suzan SeifAllah IBRAHIM

PMC · DOI: 10.1590/1678-7757-2025-0188 · Journal of Applied Oral Science · 2025-08-11

## TL;DR

Bee venom shows anti-cancer effects on tongue cancer cells by stopping cell division, causing cell death, and reducing cell movement.

## Contribution

This study is the first to demonstrate bee venom's anti-cancer effects on tongue carcinoma cells through multiple mechanisms.

## Key findings

- Bee venom caused dose-dependent cell death in tongue carcinoma cells with an IC50 of 12.96 μg/mL.
- Bee venom induced apoptosis by increasing BAX and decreasing BCL-2 gene expression.
- Bee venom reduced cell migration and caused cell cycle arrest in treated cells.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Genes:** BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596]
- **Diseases:** tongue squamous cell carcinoma (MONDO:0000500), tongue carcinoma (MONDO:0004631)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}
- **Diseases:** oral cancer (MESH:D009062), tongue carcinoma (MESH:D014062), TSCC (MESH:D000077195), cancer (MESH:D009369), cytotoxicity (MESH:D064420)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HNO-97 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_D227)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12652438/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12652438/full.md

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Source: https://tomesphere.com/paper/PMC12652438