A comparison of honeybee and scorpion venoms as anticancer agents against three different cancer cell lines: lung, colon, and breast cancer

Owing to the drawbacks and adverse effects associated with conventional cancer therapies, there is growing interest in identifying effective natural alternatives. In this study, the anticancer potential of honeybee and scorpion venoms was evaluated using three human cancer cell lines: lung adenocarcinoma (A549), colon carcinoma (HCT-116), and breast adenocarcinoma (MDA-MB-231). The chemical composition, biological activity, and molecular interactions of both venoms with key cancer-related targets were investigated through gas chromatography-mass spectrometry (GC-MS), cytotoxicity assays, gene expression analysis, and molecular docking. GC-MS analysis revealed that scorpion venom was predominantly composed of methyl isocyanide, 3-butyn-1-ol, and allene, whereas honeybee venom was characterized by caprylic anhydride, 1,3,5-triazine derivatives, and palmitin as major bioactive constituents. Functional analyses demonstrated that both venoms modulated the expression of genes associated with apoptosis and other cancer-related pathways rather than inducing apoptosis directly. Notably, scorpion venom significantly downregulated the anti-apoptotic gene <i>Bcl-2</i>, whereas honeybee venom upregulated its expression, indicating distinct mechanisms of action. Scorpion venom exerted pronounced pro-apoptotic effects, while honeybee venom appeared to act primarily through immunomodulatory and anti-angiogenic pathways. Molecular docking analyses confirmed favorable interactions between venom-derived compounds and key molecular targets, including Bcl-2, Bax, p53, and VEGF, supporting their potential as multi-target anticancer agents. Collectively, these findings demonstrate that honeybee and scorpion venoms possess promising anticancer properties via distinct yet complementary mechanisms, with particular efficacy against lung and breast adenocarcinoma cell lines. The results highlight the potential of these venoms as natural candidates for the development of alternative anticancer therapeutics.