Procyanidin C1 Inhibits Melanoma Cell Growth by Activating 67-kDa Laminin Receptor Signaling.

Abstract

SCOPE:

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.

METHODS AND RESULTS:

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.

CONCLUSION:

It is demonstrated that PC1 elicits melanoma cell growth inhibition by activating the 67LR/PKA/PP2A/CPI17/MRLC pathway.

• Authors: Jaehoon Bae, Motofumi Kumazoe, Kyosuke Murata, Yoshinori Fujimura, Hirofumi Tachibana
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 64 Issue 7 Pg. e1900986 (04 2020) ISSN: 1613-4133 [Electronic] Germany
• PMID: 32103628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavonoids
• Intracellular Signaling Peptides and Proteins
• Muscle Proteins
• Myosin Light Chains
• Ppp1r14a protein, mouse
• Receptors, Laminin
• procyanidin trimer C1
• Cyclic AMP-Dependent Protein Kinases
• Protein Phosphatase 2

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Proliferation (drug effects, physiology)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Cytoskeleton (metabolism)
• Flavonoids (pharmacology)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Melanoma, Experimental (drug therapy, metabolism, pathology)
• Mice, Inbred C57BL
• Muscle Proteins (metabolism)
• Myosin Light Chains (metabolism)
• Phosphorylation (drug effects)
• Protein Phosphatase 2 (metabolism)
• Receptors, Laminin (metabolism)