Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells
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 co...
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/50179/ |
| _version_ | 1848798176822165504 |
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| author | Sae-Lao, Thannicha Luplertlop, Natthanej Janvilisri, Tavan Tohtong, Rutaiwan Bates, David O Wongprasert, Kanokpan |
| author_facet | Sae-Lao, Thannicha Luplertlop, Natthanej Janvilisri, Tavan Tohtong, Rutaiwan Bates, David O Wongprasert, Kanokpan |
| author_sort | Sae-Lao, Thannicha |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:15:37Z |
| format | Article |
| id | nottingham-50179 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:15:37Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-501792020-05-04T19:20:49Z https://eprints.nottingham.ac.uk/50179/ 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 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. Elsevier 2017-12-01 Article PeerReviewed Sae-Lao, Thannicha, Luplertlop, Natthanej, Janvilisri, Tavan, Tohtong, Rutaiwan, Bates, David O and Wongprasert, Kanokpan (2017) Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells. Phytomedicine, 36 . pp. 59-67. ISSN 1618-095X Anti-migration ; Cholangiocarcinoma ; Epidermal growth factor receptor ; Gracilaria fisheri ; Mitogen-activated kinases/extracellular signal-regulated kinases ; Sulfated galactans https://www.sciencedirect.com/science/article/pii/S0944711317301319 doi:10.1016/j.phymed.2017.09.014 doi:10.1016/j.phymed.2017.09.014 |
| spellingShingle | Anti-migration ; Cholangiocarcinoma ; Epidermal growth factor receptor ; Gracilaria fisheri ; Mitogen-activated kinases/extracellular signal-regulated kinases ; Sulfated galactans Sae-Lao, Thannicha Luplertlop, Natthanej Janvilisri, Tavan Tohtong, Rutaiwan Bates, David O Wongprasert, Kanokpan Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title | Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title_full | Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title_fullStr | Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title_full_unstemmed | Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title_short | Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| title_sort | sulfated galactans from the red seaweed gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells |
| topic | Anti-migration ; Cholangiocarcinoma ; Epidermal growth factor receptor ; Gracilaria fisheri ; Mitogen-activated kinases/extracellular signal-regulated kinases ; Sulfated galactans |
| url | https://eprints.nottingham.ac.uk/50179/ https://eprints.nottingham.ac.uk/50179/ https://eprints.nottingham.ac.uk/50179/ |