Colon cancer is a leading cause of cancer-related deaths worldwide. Effects of walnut (Juglans regia L.) lipid extracts (WLEs) on the self-renewal capacity of cancer stem cells (CSCs) in colon cancer were investigated. The dominant component of WLEs was α-linoleic acid (64.6%), followed by α-linolenic acid (14.6%), and oleic acid (12.6%). A higher concentration of γ-tocopherol (37.1%) was also present than of α-tocopherol (0.6%). CD133+CD44+CSCs treated with WLEs showed inhibition of colony formation and sphere formation, indicating a decrease in the self-renewal capacity. Treatment with WLEs also resulted in down-regulation of protein levels, including Notch1, phospho-GSK3β (p-GSK3β), and β-catenin, which are associated with CSCs and the self-renewing capacity. WLEs rich in essential fatty acids and γ-tocopherol can exert therapeutic actions on colon cancer via targeting of CSCs.

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