Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003, Japan.
Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003, Japan.
J Lipid Res. 2019 Sep;60(9):1491-1502. doi: 10.1194/jlr.M090712. Epub 2019 Jul 25.
Fatty acids have various physiological effects on melanoma. For example, palmitic acid (PA) increases melanin levels; linoleic acid and DHA decrease melanin levels; and DHA suppresses tumor growth. In this study, we focused on the relationship between the structure of fatty acids and their physiological effects in melanoma to examine the likely mechanisms of action. We showed that saturated fatty acids and PUFAs display opposing effects on melanin content in melanoma cells. Likewise, PA and EPA have opposing effects in terms of actin polymerization. Our findings suggest that PA and EPA change melanin content in melanoma to alter melanosome trafficking by modulating actin polymerization. Here, we also examined the mechanism of the anti-tumor effect of DHA. We found that DHA interacts with receptor for activated C kinase 1 and represses melanoma cell proliferation by suppressing protein kinase C signaling. Our results suggest a new mechanism to explain the physiological effects of fatty acids.
脂肪酸对黑色素瘤有多种生理作用。例如，棕榈酸（PA）增加黑色素水平；亚油酸和 DHA 降低黑色素水平；而 DHA 则抑制肿瘤生长。在这项研究中，我们专注于脂肪酸的结构与其在黑色素瘤中的生理作用之间的关系，以探讨其可能的作用机制。我们表明，饱和脂肪酸和多不饱和脂肪酸对黑色素瘤细胞中的黑色素含量表现出相反的影响。同样，PA 和 EPA 在肌动蛋白聚合方面也有相反的作用。我们的研究结果表明，PA 和 EPA 通过调节肌动蛋白聚合来改变黑色素瘤中的黑色素含量，从而改变黑素小体的运输。在这里，我们还研究了 DHA 的抗肿瘤作用机制。我们发现 DHA 与激活的 C 激酶 1 受体相互作用，并通过抑制蛋白激酶 C 信号通路来抑制黑色素瘤细胞增殖。我们的结果提出了一种新的机制来解释脂肪酸的生理作用。
