Bee Venom and Cancer: A Mini-review Focusing on Melittin Antitumoral Effects.

Cancer remains a major concern, accounting for one in six deaths globally. Developing effective treatments is challenging due to the complex mechanisms involving environmental, genetic, and epigenetic factors. Animal toxins have been utilized as pharmacological agents for treating several diseases. Among these compounds, melittin, derived from bee venom, exhibits significant therapeutic potential against cancer. This efficacy is attributed to its multifaceted nature, enabling it to function as a multi-target modulator of oncogenic signaling pathways and exert a broad spectrum of anticancer effects. In vitro studies have demonstrated that melittin treatment reduces cell viability, adhesion, clonogenic survival, migration, and invasion in various cancer cell types. Additionally, in vitro experiments have demonstrated that melittin induces apoptosis through multiple mechanisms, such as upregulating TNF-α and BAX, triggering ferroptosis, activating the mitochondrial pathway, initiating endoplasmic reticulum stress, and inhibiting METTL3. Furthermore, in vivo assays indicate that melittin reduces angiogenesis and tumor growth, enhances the effects of chemotherapy, and prolongs survival. The effects of melittin on the tumor microenvironment, modulation of the epigenetic process, and inhibition of the epithelial-mesenchymal transition have also been demonstrated. Overall, melittin shows potential as a therapeutic agent for breast, lung, gastric, cervical, colorectal, and bladder cancers by targeting multiple pathways involved in cancer progression. Moreover, other bee venom components, such as apamin and bee venom phospholipase A2, also exhibit potential anticancer effects. In this review, a comprehensive overview of the various actions of melittin and other components of bee venom on different types of cancer is provided. The research discusses their mechanisms of action and potential strategies to enhance efficacy and minimize toxicity.