15-Lipoxygenase-1 expression suppresses the invasive properties of colorectal carcinoma cell lines HCT-116 and HT-29.
Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-Lipoxygenase-1 (15-LO-1), a member of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In this study, we investigated the hypothesis that the lack of 15-LO-1 expression in CRC cells might contribute to tumorigenesis. Therefore we introduced 15-LO-1 into HCT-116 and HT-29 cells that do not have detectable levels of 15-LO-1. Our data indicate that expression of 15-LO-1 significantly decreased cell proliferation and increased apoptosis. In addition, we observed a reduction in adhesion to fibronectin, anchorage-independent growth on soft agar, cellular motility and ability to heal a scratch wound, and migratory and invasive capacity across Matrigel. 15-LO-1 expression also reduced the expression of metastasis associated protein-1, a part of the nucleosome remodeling and histone deacetylase silencing complex. We propose that 15-LO-1 expression in CRC might contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes.
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.
Ismail
I
Cimen
Seda
S
Tunçay
Sreeparna
S
Banerjee
D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D045325:HCT116 Cells; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D008041:Linoleic Acids / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012097:Repressor Proteins / Q000502:physiology; D015534:Trans-Activators
D008041:Linoleic Acids; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C024348:13-hydroxy-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase; D006655:Histone Deacetylases