Involvement of 67-kDa laminin receptor-mediated myosin phosphatase activation in antiproliferative effect of epigallocatechin-3-O-gallate at a physiological concentration on Caco-2 colon cancer cells.
Previously we reported that 67-kDa laminin receptor (67LR) mediates epigallocatechin-3-O-gallate (EGCG)-induced cell growth inhibition and reduction of myosin regulatory light chain (MRLC) phosphorylation at Thr-18/Ser-19, which is important for cytokinesis. Here, we found that human colon adenocarcinoma Caco-2 cells exhibited higher expression level of 67LR and EGCG at a physiologically achievable concentration (1 microM) significantly accumulated the cells in G(2)/M phase without affecting expression of Wnt-signaling components. We also found that myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation at Thr-696, which inhibits myosin phosphatase and promotes MRLC phosphorylation, was reduced in response to 1 microM EGCG. 67LR knockdown by RNA interference abolished the inhibitory effects of 1 microM EGCG on cell cycle progression and the phosphorylation of MRLC and MYPT1. These results suggest that through 67LR, EGCG at a physiological concentration can activate myosin phosphatase by reducing MYPT1 phosphorylation and that may be involved in EGCG-induced cell growth inhibition.
Umeda
Daisuke
D
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Yano
Satomi
S
Yamada
Koji
K
Tachibana
Hirofumi
H
D000230:Adenocarcinoma / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D043263:Myosin-Light-Chain Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D017474:Receptors, Laminin; D002392:Catechin; C045651:epigallocatechin gallate; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human