Anti-tumor activity of beauvericin: focus on intracellular signaling pathways

Beauvericin, a Fusarium mycotoxin commonly found in feeds, particularly cereals worldwide, exhibits a wide array of biofunction. It exhibits anticancer characteristics in addition to its antiviral, antifungal and antibacterial capabilities against gram-positive and gram-negative microorganisms. The mechanism underlying most of beauvericin's properties lies in its ionophoric activity. By facilitating calcium (Ca²⁺) flow from the extracellular space as well as its release from intracellular reservoirs, beauvericin increases intracellular free Ca²⁺. This elevation in Ca²⁺ levels leads to detrimental effects on mitochondria and oxidative stress, ultimately resulting in apoptosis and cell death. Studies on various cancer cell lines have shown that beauvericin induces apoptosis upon exposure. Moreover, besides its cytotoxic effects, beauvericin also inhibits cancer growth and progression by exerting anti-angiogenic and anti-migratory effects on cancer cells. Additionally, beauvericin possesses immunomodulatory properties, albeit less explored. Recent research indicates its potential to enhance the maturation and activation of dendritic cells (DCs) and T cells, both directly through its interaction with Toll-like receptor 4 (TLR4) and indirectly by increasing intracellular Ca²⁺ levels. Hence, beauvericin could serve as an adjuvant in chemoimmunotherapy regimens to enhance treatment outcomes. Given these diverse properties, beauvericin emerges as an intriguing candidate for developing effective cancer treatments. This review explores the cellular signaling pathways involved in its anticancer effects.