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The toxicity of bovine α‐lactalbumin made lethal to tumor cells is highly dependent on oleic acid and induces killing in cancer cell lines and noncancer‐derived primary cells

A complex between α‐lactalbumin and oleic acid (C18:1, 9 cis) has been reported to be cytotoxic to cancer cells. We have prepared such complexes and tested their activity against both cancer cell lines and noncancer‐derived primary cells. Unexpectedly, some primary cell types were more sensitive to treatment than cancer cell lines. We found the complex to be cytotoxic to all of the tested cells, with a 46‐fold difference between the most sensitive and the least sensitive cell type. Oleic acid by itself exhibited a remarkably similar activity. The cell‐killing mechanisms of the complex and of oleic acid alone were examined by flow cytometry, testing for apoptosis‐ and necrosis‐ inducing activity. The T‐cell leukemia‐derived Jurkat cells primarily underwent cell death resembling apoptosis, whereas the monocytic leukemia‐derived THP1 cells adopted a more necrotic‐like cell death. Erythrocytes were sensitive to lysis by the complex and oleic acid. We conclude that oleic acid is cytotoxic by itself and that, in contrast to the literature, a complex of α‐lactalbumin and oleic acid has cytotoxic activity against primary cells, as well as cancer cells.