title: Fucoxanthin Activates Apoptosis via Inhibition of PI3K/Akt/mTOR Pathway and Suppresses Invasion and Migration by Restriction of p38-MMP-2/9 Pathway in Human Glioblastoma Cells.
abstract: Fucoxanthin is rich in seaweed and considered as effective anti-cancer drug because of powerful antioxidant properties. The objective of this study was to investigate the role of fucoxanthin on apoptosis, invasion and migration of glioma cells. Firstly, fucoxanthin showed obvious cytotoxicity against human glioma cancer cell line U87 and U251, however, there was no inhibitory effect on normal neuron. And then, fucoxanthin induced apoptotic cell death showed by the condensation of chromatin material stained with Hoechest 33342, and reduced mitochondrial membrane potential via DIOC6(3) staining, and enhanced apoptosis by annexin V-FITC/SYTOX Green double staining on U87 and U251 cell lines. Transmission electron microscopy and western blotting were used to determine ultrastructure of U87 cell and expression of proteins related to apoptosis. A scratch wound healing assay and the expression of matrix metalloproteinases (MMPs), and a tans-well assay were used to investigate cell migration and invasion, respectively. Additionally, we uncovered upstream signaling Akt/mTOR and p38 pathways induced by incubation U87 and U251 cell lines with fucoxanthin that mediated cell apoptosis, migration and invasion by using PI3K and p38 inhibitors. Moreover, incubation of fucoxanthin obviously reduced the weight and volume of glioma mass of U87 cells in nude mice. Furthermore, we also examined the glioma mass of U87 cells by hematoxylin-eosin staining, TUNEL assay and western blot, and these outcomes in vivo consistently confirmed that above results in vitro. Taken together, these findings suggest that fucoxanthin augments apoptosis, and reduces cell proliferation, migration and invasion, and reveals a potential mechanism of fucoxanthin-mediated Akt/mTOR and p38 susspression in human glioblastoma cell line.
authors.affiliation: Affiliated Bayi Brain Hospital and Affiliated Beijing Military General Hospital of Southern Medical University, Beijing, 100070, China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Dezhou People Hospital, Jinan, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Affiliated Bayi Brain Hospital and Affiliated Beijing Military General Hospital of Southern Medical University, Beijing, 100070, China.
authors.forename: Zhaotao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing, Beijing, China.
authors.forename: Miaochun
authors.initials: M
authors.lastname: Bai
authors.affiliation: Affiliated Bayi Brain Hospital and Affiliated Beijing Military General Hospital of Southern Medical University, Beijing, 100070, China. dyw100200@163.com.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005910:Glioma / Q000188:drug therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D024341:Xanthophylls; D048051:p38 Mitogen-Activated Protein Kinases; C025164:fucoxanthin; C546843:mTOR protein, mouse; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: Apoptosis; Fucoxanthin; Invastion; Migration; P38; PI3K/Akt/mTOR; U87 and U251