The dietary phytochemical chlorophyllin alters E-cadherin and beta-catenin expression in human colon cancer cells.
Chlorophyllin (CHL), an anticarcinogenic and antimutagenic water-soluble derivative of chlorophyll, has been reported to induce apoptosis in human colon cancer cells via a pathway involving cell differentiation. Induction of differentiation markers may be important in limiting cancer-cell invasion and metastasis, and there is much interest in understanding the underlying mechanisms, because this might provide insights for cancer chemotherapy. In the present study, human HCT116 colon-cancer cells were treated with CHL, and the expression levels of E-cadherin and beta-catenin were examined using immunocytochemistry and laser scanning confocal microscopy. E-cadherin was detected almost exclusively at the cell periphery of cancer cells treated with or without CHL, but the expression of E-cadherin in the plasma membrane was markedly elevated in the cells treated with CHL. beta-Catenin also was strongly expressed in the plasma membrane, especially after CHL treatment. No change in the expression of beta-catenin mRNA was detected across a broad range of CHL concentrations (10-500 micromol/L), but there was a concentration-dependent decrease in nuclear beta-catenin protein levels without overt changes in the cytosolic pool of beta-catenin. Our interpretation of these findings is that CHL induces E-cadherin expression, and this facilitates trafficking of beta-catenin away from the nucleus and into the plasma membrane, possibly for destruction via the adherins junction remodeling (Hakai) pathway.
Carter
Orianna
O
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Bailey
George S
GS
Dashwood
Roderick H
RH
D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D002735:Chlorophyllides / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; D002735:Chlorophyllides; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; C007020:chlorophyllin