Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Hsin Yuan Chen, Tsui Chin Huang, Li Chun Lin, Tzong Ming Shieh, Chi Hao Wu, Kai Lee Wang, Yong Han Hong, Shih Min Hsia

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

Original languageEnglish
Pages (from-to)1970-1986
Number of pages17
JournalCellular Physiology and Biochemistry
Volume49
Issue number5
DOIs
Publication statusPublished - Oct 1 2018

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Extracellular Matrix Proteins
Leiomyoma
Cell Proliferation
Heterografts
Neoplasms
Growth
Side-Population Cells
Apoptosis
G1 Phase Cell Cycle Checkpoints
Gentian Violet
fucoidan
Seaweed
Catenins
Myometrium
Vimentin
Fibronectins
Nude Mice
Transforming Growth Factor beta
Smooth Muscle Myocytes
Extracellular Matrix

Keywords

  • Uterine leiomyoma • Fucoida • Transforming growth factor beta • Extracellular matrix • ELT-3-LUC • Xenograft model

ASJC Scopus subject areas

  • Physiology

Cite this

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression. / Chen, Hsin Yuan; Huang, Tsui Chin; Lin, Li Chun; Shieh, Tzong Ming; Wu, Chi Hao; Wang, Kai Lee; Hong, Yong Han; Hsia, Shih Min.

In: Cellular Physiology and Biochemistry, Vol. 49, No. 5, 01.10.2018, p. 1970-1986.

Research output: Contribution to journalArticle

Chen, Hsin Yuan ; Huang, Tsui Chin ; Lin, Li Chun ; Shieh, Tzong Ming ; Wu, Chi Hao ; Wang, Kai Lee ; Hong, Yong Han ; Hsia, Shih Min. / Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression. In: Cellular Physiology and Biochemistry. 2018 ; Vol. 49, No. 5. pp. 1970-1986.
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T1 - Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

AU - Chen, Hsin Yuan

AU - Huang, Tsui Chin

AU - Lin, Li Chun

AU - Shieh, Tzong Ming

AU - Wu, Chi Hao

AU - Wang, Kai Lee

AU - Hong, Yong Han

AU - Hsia, Shih Min

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AB - Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

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