Octacosanol inhibits tumor metastasis and invasion by targeting MMPs via PI3K/AKT and MAPK signaling pathways

Octacosanol, a natural long-chain fatty alcohol widely present in dietary sources such as rice bran and sugarcane wax, demonstrates considerable bioactive properties with relevance to human health. This study explored the anti-tumor effects and underlying mechanisms of octacosanol in osteosarcoma, with a focus on its regulatory impact on critical pathways involved in cancer progression – specifically metastasis and angiogenesis – from the perspective of food-derived bioactive compounds. Notably, under non-cytotoxic conditions, octacosanol significantly reduced tumor cell metastasis and invasion by downregulating both the expression and activity of matrix metalloproteinases (MMPs), mediated through modulation of the PI3K/AKT, MAPK, and NF-κB pathways. Moreover, octacosanol effectively inhibited tumor angiogenesis by decreasing vascular endothelial growth factor (VEGF) secretion from tumor cells and suppressing VEGF receptor 2 (VEGFR2) phosphorylation and its downstream signaling in endothelial cells. In vivo experiments demonstrated that octacosanol treatment significantly prolonged survival in primary osteosarcoma mice and decreased the expression of key metastasis-related proteins (p-AKT, MMP2, MMP9) and angiogenesis markers (CD34, VEGF, p-VEGFR2). These findings indicate that octacosanol, a dietary bioactive compound, effectively slows osteosarcoma progression by inhibiting both metastasis and angiogenesis. Thus, it is a promising functional food ingredient with potential for use in nutrition-based cancer prevention and health support strategies. • Unraveling the anti-tumor effects and molecular mechanisms of octacosanol. • Inhibition of primary osteosarcoma metastasis and angiogenesis by octacosanol. • Octacosanol effectively regulates PI3K/AKT and MAPK signalling pathways. • Octacosanol targets MMP2 and MMP9 to inhibit tumor cell metastasis. • Anti-tumor angiogenesis by inhibiting VEGF expression and VEGFR2 activation.