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Neurochemical Research

, Volume 41, Issue 10, pp 2728–2751 | Cite as

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

  • Yugang Liu
  • Jian Zheng
  • Yan Zhang
  • Zhaotao Wang
  • Yang Yang
  • Miaochun Bai
  • Yiwu Dai
Original Paper

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.

Keywords

Fucoxanthin U87 and U251 Apoptosis Invastion Migration PI3K/Akt/mTOR P38 

Notes

Acknowledgments

This research was supported by Natural Science Foundation of China (NSFC-81271391).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yugang Liu
    • 1
  • Jian Zheng
    • 2
  • Yan Zhang
    • 3
  • Zhaotao Wang
    • 1
  • Yang Yang
    • 4
  • Miaochun Bai
    • 3
  • Yiwu Dai
    • 1
  1. 1.Affiliated Bayi Brain Hospital and Affiliated Beijing Military General Hospital of Southern Medical UniversityBeijingChina
  2. 2.Department of PathologyDezhou People HospitalJinanChina
  3. 3.Affiliated Bayi Brain Hospital, The Military General Hospital of BeijingBeijingChina
  4. 4.Dalian Medical UniversityDalianChina

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