Epigallocatechin-3-O-gallate disrupts stress fibers and the contractile ring by reducing myosin regulatory light chain phosphorylation mediated through the target molecule 67 kDa laminin receptor.
Epigallocatechin-3-O-gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit the growth of various cancer cell lines. We show here that EGCG induced the disruption of stress fibers and decreased the phosphorylation of the myosin II regulatory light chain (MRLC) at Thr18/Ser19, which is necessary for both contractile ring formation and cell division. Indirect immunofluorescence analysis revealed that EGCG inhibited the concentration of both F-actin and the phosphorylated MRLC in the cleavage furrow at the equator of dividing cells. In addition, EGCG increased the percentages of cells in the G(2)/M phase and inhibited cell growth. Recently, we have demonstrated that the anticancer activity of EGCG is mediated by the metastasis-associated 67kDa laminin receptor (67LR). To explore whether the effect of EGCG is mediated by the 67LR, we transfected cells with short hairpin RNA (shRNA) expression vector to downregulate 67LR expression. When the 67LR was silenced, the suppressive effect of EGCG on the MRLC phosphorylation was significantly attenuated. These results suggest that EGCG inhibits the cell growth by reducing the MRLC phosphorylation and this effect is mediated by the 67LR.
Umeda
Daisuke
D
Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
Tachibana
Hirofumi
H
Yamada
Koji
K
D000199:Actins / Q000378:metabolism*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D049109:Cell Proliferation / Q000187:drug effects*; D003285:Contractile Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017474:Receptors, Laminin / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism*
D000199:Actins; D003285:Contractile Proteins; C466107:MRLC2 protein, human; D018994:Myosin Light Chains; D017474:Receptors, Laminin; D002392:Catechin; C045651:epigallocatechin gallate