Bovine lactoferrin drives cell cycle arrest and alters the transcriptomic profile of NSCLC cells.

Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. NSCLC is less sensitive to conventional chemotherapeutic agents, and high mortality and recurrence rates have become the impetus to find alternative therapies. Bovine lactoferrin (bLF) derived from bovine milk, has been shown to inhibit lung cancer growth through inhibiting angiogenesis and dampening inflammation in vivo. However, the mechanism by which bLF does this within the context of lung cancer is not well understood. Our study aims to untangle these mechanistic details to provide a biochemical and transcriptomic landscape in lung cancer cells treated with bLF. Treatment with bLF significantly decreased the viability of A549 and H-1299 lung carcinoma cells. In NSCLC cells, bLF induced S-phase cell cycle arrest and suppressed migratory capacity. Importantly, research findings bLF triggered mitochondrial dysfunction and apoptotic cell death via the intrinsic mitochondrial apoptotic pathway. Importantly, RNA sequencing revealed major transcriptomic changes in bLF treated cells, particularly in the focal adhesion, cell cycle, and proteoglycans in cancer pathways. Our findings further emphasizes the potent anti-cancer properties of bLF and highlight the potential for bLF as a natural product-derived alternative therapy for NSCLC.