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Spirulina phycocyanin extract and its active components suppress epithelial-mesenchymal transition process in endometrial cancer via targeting TGF-beta1/SMAD4 signaling pathway - 18/06/22

Doi : 10.1016/j.biopha.2022.113219 
Hsin-Yuan Chen a, b, Yi-Fen Chiang a, Chun-Yung Huang c, Tzong-Ming Shieh d, Chieh Kao e, Fu-Kuei Chang f, Tsui-Chin Huang g, Mohamed Ali h, Hsin-Yi Chang i, Yong-Han Hong b, ⁎ , Shih-Min Hsia a, j, k, l, ⁎
a School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan 
b Department of Nutrition, I-Shou University, Kaohsiung 84001, Taiwan 
c Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan 
d School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan 
e School of Medicine for International Students, I-Shou University, Kaohsiung 82445, Taiwan 
f Department of Health Management, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan 
g Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan 
h Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt 
i Graduate Institute of Medical Science, National Defense Medical Center, Taipei 114, Taiwan 
j School of Food and Safety, Taipei Medical University, Taipei 11031, Taiwan 
k Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan 
l Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan 

⁎Corresponding author.⁎⁎Corresponding author at: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical UniversityTaipei11031Taiwan

Abstract

Metastasis is a major challenge in aggressive endometrial cancer treatment accounting for the high recurrence risk and poor prognosis of epithelial–mesenchymal transition (EMT), regulated by the transforming growth factor beta (TGFβ) signaling pathway, facilitates tumor metastasis. Spirulina phycocyanin extract (SPE) and its purified products allophycocyanin (APC) and C-phycocyanin (C-PC), derived from Spirulina platensis, can be considered a nutraceutical compound with the ability to inhibit tumor growth and metastasis. Current study aims to investigate the anti-metastatic potential of SPE, and its purified products APC, and C-PC on endometrial cancer both in vitro and in vivo. Firstly, human endometrial cancer cell lines (HEC-1A and Ishikawa) as an in vitro model. Secondly, HEC-1A cells transfected with luminescence gene were implanted into female nude mice as a xenograft model. MTT assay, transwell migration assay, immunoblotting assay, quantitative real-time polymerase chain reaction assay, and IVIS XRMS analysis techniques were used. The in vitro results showed that SPE and its purified products APC and C-PC inhibited cell migration, and altered the expression of EMT-related phenotypes by reversing the TGFβ/SMADs signaling pathway. The in vivo results indicated that SPE repressed the metastasis of HEC-1A-LUC cells through modulating EMT-related markers expression. Overall, SPE and its efficient components APC and C-PC reversed the EMT through targeting the TGFβ/SMADs signaling pathway, suggesting an effective therapeutic strategy for metastatic endometrial cancer.

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Graphical Abstract




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El texto completo de este artículo está disponible en PDF.

Highlights

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This is the first study to investigate whether SPE affect the metastatic effect of invasive endometrial cancer.
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SPE could reducing the migration of endometrial cancer cells and reducing tumor metastasis in nude mice.
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The mechanism of SPE involve a reversal of the expression of epithelial-mesenchymal transition-related proteins and genes.

El texto completo de este artículo está disponible en PDF.

Abbreviations : EC, TGFβ, EMT, SPE, APC, C-PC, R-SMADs, SNAI1, SLUG, ZEB1/2, TWIST1/2, α-SMA, TMEFF2, IVIS XRMS

Keywords : Endometrial cancer, spirulina phycocyanin extract, Allophycocyanin, C-phycocyanin, Epithelial–mesenchymal transition, Transforming growth factor beta


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© 2022  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 152

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