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Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells

Sae-Lao, Thannicha; Luplertlop, Natthanej; Janvilisri, Tavan; Tohtong, Rutaiwan; Bates, David O; Wongprasert, Kanokpan

Authors

Thannicha Sae-Lao

Natthanej Luplertlop

Tavan Janvilisri

Rutaiwan Tohtong

Kanokpan Wongprasert



Abstract

BACKGROUND: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells.
PURPOSE: In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism.
METHODS: CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators.
RESULTS: Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK.
CONCLUSION: This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment.

Citation

Sae-Lao, T., Luplertlop, N., Janvilisri, T., Tohtong, R., Bates, D. O., & Wongprasert, K. (2017). Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells. Phytomedicine, 36, https://doi.org/10.1016/j.phymed.2017.09.014

Journal Article Type Article
Acceptance Date Sep 24, 2017
Online Publication Date Sep 28, 2017
Publication Date Dec 1, 2017
Deposit Date Mar 5, 2018
Publicly Available Date Sep 29, 2018
Journal Phytomedicine
Print ISSN 0944-7113
Electronic ISSN 1618-095X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 36
DOI https://doi.org/10.1016/j.phymed.2017.09.014
Keywords Anti-migration ; Cholangiocarcinoma ; Epidermal growth factor receptor ; Gracilaria fisheri ; Mitogen-activated kinases/extracellular signal-regulated kinases ; Sulfated galactans
Public URL http://eprints.nottingham.ac.uk/id/eprint/50179
Publisher URL https://www.sciencedirect.com/science/article/pii/S0944711317301319
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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