Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan.
Mol Nutr Food Res. 2020 Apr;64(7):e1900986. doi: 10.1002/mnfr.201900986. Epub 2020 Mar 6.
Procyanidin C1 (PC1) is an epicatechin trimer found mainly in grapes that is reported to provide several health benefits. However, little is known about the molecular mechanisms underlying these benefits. The aim of this study is to demonstrate the molecular mechanisms by which PC1 operates.
A 67-kDa laminin receptor (67LR) is identified as a cell surface receptor of PC1, with a Kd value of 2.8 µm. PC1 induces an inhibitory effect on growth, accompanied by dephosphorylation of the C-kinase potentiated protein phosphatase-1 inhibitor protein of 17 kDa (CPI17) and myosin regulatory light chain (MRLC) proteins, followed by actin cytoskeleton remodeling in melanoma cells. These actions are mediated by protein kinase A (PKA) and protein phosphatase 2A (PP2A) activation once PC1 is bound to 67LR.
It is demonstrated that PC1 elicits melanoma cell growth inhibition by activating the 67LR/PKA/PP2A/CPI17/MRLC pathway.
原花青素 C1（PC1）是一种主要存在于葡萄中的表儿茶素三聚体，据报道具有多种健康益处。然而，对于这些益处背后的分子机制知之甚少。本研究旨在阐明 PC1 作用的分子机制。
鉴定出 67 kDa 层粘连蛋白受体（67LR）是 PC1 的细胞表面受体，Kd 值为 2.8 µm。PC1 诱导生长抑制，伴随 C-激酶增强的蛋白磷酸酶-1 抑制剂蛋白 17 kDa（CPI17）和肌球蛋白调节轻链（MRLC）蛋白的去磷酸化，随后在黑色素瘤细胞中肌动蛋白细胞骨架重塑。这些作用是通过一旦 PC1 与 67LR 结合，蛋白激酶 A（PKA）和蛋白磷酸酶 2A（PP2A）的激活介导的。
证明 PC1 通过激活 67LR/PKA/PP2A/CPI17/MRLC 途径引发黑色素瘤细胞生长抑制。
