Bee venom and its major component, melittin exhibit potent anticancer effects against breast cancer through diverse mechanisms of action. Melittin induces rapid cell death via membrane disruption and triggers apoptosis through both intrinsic and extrinsic pathways by activating caspases, modulating Bcl-2 family proteins, and generating reactive oxygen species. Unmodified melittin delivery causes necrosis and stimulates autophagic cell death on higher concentration. Additionally, bee venom inhibits angiogenesis by targeting the VEGF/VEGFR-2 signaling axis and suppresses metastasis by downregulating matrix metalloproteinases, inhibiting cell migration and invasion, and reversing epithelial-to-mesenchymal transition. These effects are mediated through the modulation of key signaling pathways, including PI3K/Akt/mTOR, MAPK, and NF-κB. Notably, Melittin enhance the efficacy of conventional therapies, such as chemotherapy, radiotherapy, and hormonal therapy, while reducing systemic toxicity and drug resistance. However, clinical translation is hindered by challenges such as dose-dependent toxicity, off-target effects, and potential allergic reactions. Nanoformulations, including liposomes, micelles, and polymeric nanoparticles, have emerged as promising strategies to overcome these limitations by improving stability, tumor targeting, and controlled release. Preclinical studies in breast cancer cell lines and animal models have demonstrated significant tumor suppression and reduced metastasis with bee venom and melittin-based treatments. While preliminary clinical evidence is limited, ongoing research aims to harness the therapeutic potential of bee venom through molecular engineering and advanced drug delivery systems, paving the way for novel, nature-inspired approaches in the fight against breast cancer. • Bee venom and melittin exhibit potent anticancer effects against breast cancer through diverse mechanisms. • Melittin induces apoptosis, necrosis, and autophagy in breast cancer cells via multiple pathways. • Bee venom inhibits angiogenesis by targeting VEGF/VEGFR-2 and suppresses metastasis by downregulating MMPs. • Key signaling pathways modulated by bee venom include PI3K/Akt/mTOR, MAPK, and NF-κB. • Bee venom enhances the efficacy of chemotherapy, radiotherapy, and hormonal therapy while reducing toxicity. • Nanoformulations such as liposomes and polymeric nanoparticles improve stability, targeting, and controlled release. • Preclinical studies demonstrate significant tumor suppression and reduced metastasis with bee venom-based treatments.
Thirugnanam et al. (Wed,) studied this question.