Abstract
Honeybees play a crucial ecological and economic role by pollinating both natural ecosystems and cultivated crops. Beyond this, they produce such valuable natural products as honey, propolis, royal jelly, bee pollen, beeswax, and bee venom, which have been used for centuries in traditional medicine. With the growing interest in natural compounds for disease prevention and treatment, apitherapy and bee-derived products have gained renewed attention. Among these, bee venom (BV) stands out due to its rich composition of bioactive molecules, including peptides such as melittin, phospholipase A2 (PLA2), apamin, mast cell degranulation peptide, secapin, and adolapin, as well as enzymes as hyaluronidase. These components are known for their therapeutic potential, particularly in inflammation and cancer-related applications. In this study, the cytotoxic and apoptosis-inducing effects of Apis mellifera L. venom samples collected from fifty-one locations across Türkiye were tested against seven human cancer cell lines (Caco-2, PC3, U-87MG, MDA-MB-231, A549, HeLa, Panc-1) and one healthy line (CCD-34Lu). Cytotoxicity was assessed with use of the MTT assay, and IC50 values ranged from 1.64±0.70 to 98.33±9.28 µg/ml. Venoms from Maçahel, Faraşin, Kırklareli, Düzce, Adana, Hatay, and Gökçeada were the most potent, influenced by bee ecotypes and protein content. PC3, PANC-1, and HeLa were the most sensitive cell lines, while Caco-2 and CCD-34Lu showed the highest resistance. In conclusion, the diverse venoms of A. mellifera in Türkiye exhibit significant dose-dependent cytotoxic and apoptotic effects, positioning the country as a valuable source in venom-based therapeutic research.