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Microalgal extract from thermotolerant Coelastrella sp. F50 retards the liver tumor progression by targeting hepatic cancer stem cells
Author(s) -
Chang YiChen,
Chu TianHuei,
Yu PoChien,
Wang EMing,
Huang ChaoCheng,
Hu TsungHui,
Wen ZhiHong,
Ko ChouYuan,
Chen ChingNen Nathan,
Tai MingHong
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7111
Subject(s) - cancer stem cell , population , liver cancer , side population , hepatocellular carcinoma , pharmacology , cancer research , hepatocyte , chemistry , stem cell , in vitro , biology , medicine , biochemistry , microbiology and biotechnology , environmental health
Microalgae extracts have shown antitumor activities. However, the antitumor mechanism of them is not yet completely clear, especially the effect on cancer stem cells (CSCs). This study aimed to elucidate the antitumor activity and mechanism of microalgal extract from thermotolerant Coelastrella sp. F50 (F50) in hepatocellular carcinoma (HCC). Oncogenic behaviors were analyzed using cell proliferation, colony formation, invasion, sphere formation, and side population cells (SPCs) assays in HCC cells after F50 treatment. The molecular mechanism was further studied by quantitative real‐time PCR , immunoblot, and immunofluorescence analyses. The chemopreventive efficacy of F50 was evaluated in rat orthotopic hepatoma, and the hepatic pathologies were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. F50 specifically suppressed hepatic CSCs (tumor spheres, drug efflux, CD133/ABCG2 CSCs markers) with no cytotoxicity in vitro . In the animal experiments, prophylactic F50 administration significantly attenuated tumor progression and improved liver function in HCC‐bearing rats. In the mechanistic analysis, F50 potentially inhibited cyclooxygenase‐2 (COX‐2)/prostaglandin E2 (PGE 2 ) axis in HCC cells and rat hepatoma, and exogenous PGE 2 restored CSCs properties in F50‐treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX‐2/PGE 2 downregulation and may facilitate a novel phytotherapy for HCC prevention.