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https://ir.cnu.edu.tw/handle/310902800/34849
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| 標題: | The in vitro and in vivo anticancer activities of Antrodia salmonea through inhibition of metastasis and induction of ROS-mediated apoptotic and autophagic cell death in human glioblastoma cells |
| 作者: | Lin, Yi-Pin
Hseu, You-Cheng
Thiyagarajan, Varadharajan
Vadivalagan, Chithravel
Pandey, Sudhir
Lin, Kai-Yuan
Hsu, Yuan-Tai
Liao, Jiunn-Wang
Lee, Chuan-Chen
Yang, Hsin-Ling |
| 貢獻者: | China Med Univ, Inst Nutr, Coll Hlth Care
China Med Univ, Coll Pharm, Dept Cosmeceut, Shui Nan Campus
Asia Univ, Dept Hlth & Nutr Biotechnol
China Med Univ, Chinese Med Res Ctr
China Med Univ, Res Ctr Chinese Herbal Med
Mahidol Univ, Fac Pharm, Dept Pharmacol
Chi Mei Med Ctr, Dept Med Res
Chia Nan Univ Pharm & Sci, Dept Biotechnol
Natl Chung Hsing Univ, Grad Inst Vet Pathol |
| 關鍵字: | Antrodia salmonea
Glioblastoma
Autophagy
Apoptosis
ROS
EMT |
| 日期: | 2023 |
| 上傳時間: | 2024-12-25 11:04:29 (UTC+8) |
| 出版者: | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 摘要: | Background:: Antrodia salmonea (AS) exhibits anticancer activities against various cancers.Objective: This study investigated the anticancer activities of AS on human glioblastoma (GBM8401 and U87MG) cells both in vitro and in vivo and explained the underlying molecular mechanism.Methods: MTT, colony formation, migration/invasion assay, immunoblotting, immunofluorescence, TUNEL, Annexin V/PI staining, AO staining, GFP-LC3 transfection, TEM, qPCR, siLC3, DCFH2-DA assay, and xenograftednude mice were used to assess the potential of AS therapy.Results: AS treatment retarded growth and suppressed colony formation in glioblastoma cells. AS attenuates EMT by suppressing invasion and migration, increasing E-cadherin expression, decreasing Twist, Snail, and N-cadherin expression, and inhibiting Wnt/beta-catenin pathways in GBM8401 and U87MG cells. Furthermore, AS induced apoptosis by activating caspase-3, cleaving PARP, and dysregulating Bax and Bcl-2 in both cell lines. TUNEL assay and Annexin V/PI staining indicated AS-mediated late apoptosis. Interestingly, AS induced autophagic cell death by LC3-II accumulation, AVO formation, autophagosome GFP-LC3 puncta, p62/SQSTM1 expression, and ATG4B inhibition in GBM8401 and U87MG cells. TEM data revealed that AS favored autophagosome and autolysosome formation. The autophagy inhibitors 3-MA/CQ and LC3 knockdown suppressed AS-induced apoptosis in glioblastoma cells, indicating that the inhibition of autophagy decreased AS-induced apoptosis. Notably, the antioxidant N-acetylcysteine (NAC) inhibited AS-mediated ROS production and AS induced apoptotic and autophagic cell death. Furthermore, AS induced ROS-mediated inhibition of the PI3K/ AKT/mTOR signaling pathway. AS reduced the tumor burden in GBM8401-xenografted nude mice and significantly modulated tumor xenografts by inducing anti-EMT, apoptosis, and autophagy. AS could be a potential antitumor agent in human glioblastoma treatment. |
| 關聯: | Biomedicine & Pharmacotherapy, v.158, Article 114178 |
| 顯示於類別: | [行政單位] 456
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