Tris(8-Hydroxyquinoline)iron induces apoptotic cell death via oxidative stress and by activating death receptor signaling pathway in human head and neck carcinoma cells

doi:10.1016/j.phymed.2019.153005

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 化妝品應用與管理系(所) > 期刊論文 > Item 310902800/32657

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標題:	Tris(8-Hydroxyquinoline)iron induces apoptotic cell death via oxidative stress and by activating death receptor signaling pathway in human head and neck carcinoma cells
作者:	Chan, Leong-Perng Tseng, Ya-Ping Hsiou-Yu Ding(丁秀玉) Pan, Sheng-Ming Chiang, Feng-Yu Wang, Ling-Feng Chou, Tzung-Han Lien, Pei-Jung Liu, Cheng Kuo, Po-Lin Chia-Hua Liang(梁家華)
貢獻者:	Kaohsiung Med Univ, Kaohsiung Municipal Ta Tung Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Coll Med, Fac Med Kaohsiung Med Univ, Grad Inst Clin Med Natl Cheng Kung Univ, Inst Basic Med Sci Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Chia Nan Univ Pharm & Sci, Inst Cosmet Sci Nat Chung Shan Inst Sci & Technol, Chem Syst Res Div Propellant Plant Natl Yunlin Univ Sci & Technol, Dept Chem & Mat Engn, Touliu Met Ind Res & Dev Ctr Shu Zen Jr Coll Med & Managemen4, Dept Dent Technol Natl Sun Yat Sen Univ, Inst Med Sci & Technol
關鍵字:	Tris(8-Hydroxyquinoline)iron Human head and neck carcinoma Oxidative stress Mitochondria Death receptor
日期:	2019-10
上傳時間:	2020-07-29 13:54:01 (UTC+8)
出版者:	ELSEVIER GMBH
摘要:	Background: 8-Hydroxyquinoline derivatives have highly sensitive fluorescent chemosensors for metal ions, which are associated with anti-oxidant, anti-tumor and anti-HIV-1 properties. Head and neck squamous cell carcinoma (HNSCC) is associated with a high rate of mortality and novel anti-HNSCC drugs must be developed. Therefore, effective chemotherapy agents are required to address this public health issue. Hypothesis/Purpose: The aim of this study was to investigate the inhibitory effect of tris(8-hydroxyquinoline)iron (Feq(3)) on the HNSCC and the underlying mechanism. Study design/Methods: A novel 8-hydroxyquinoline derivative, Feq(3), was synthesized. The cell viabilities were analyzed using MTT reagent. Apoptosis and the cell cycle distributions were determined by flow cytometer. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, western blot, MitoSOX and CellROX stain assay were used to study the mechanism of Feq(3). Feq(3) combined with antioxidants NAC (N-acetylcysteine) and BSO (buthionine sulfoximine) measured the cell viability and intracellular ROS. Results: Feq(3) induced the death of HNSCC cells and caused them to exhibit the morphological features of apoptosis. Feq(3) also induced apoptosis of SCC9 cells by cell cycle arrest during the G(2)/M phase and the induced arrest of SCC25 cells in the G(0)/G(1) and G(2)/M phases, which was associated with decreased cyclin B1/cdc2 and cyclin D/cdk4 expressions. Feq(3) increases reactive oxygen species (ROS) and reduces glutathione (GSH) levels, and responds to increased p53 and p21 expressions. Feq(3) induced apoptosis by mitochondria-mediated Box and cytochrome c up-expression and down-expression Bcl-2. Feq(3) also up-regulated tBid, which interacts with the mitochondrial pathway and tumor necrosis factor-alpha (TNF-alpha)/TNF-Rs, FasL/Fas, and TNF-related apoptosis inducing ligand receptors (TRAIL-Rs)/TRAIL-dependent caspases apoptotic signaling pathway in HNSCC cells. However, Feq(3) activates Fas but not FasL in SCC25 cells. Feq(3) arrests the growth of HNSCC cells and is involved in the mitochondria- and death receptor (DR)-mediated caspases apoptotic pathway. Conclusion: This study is the first to suggest that apoptosis mediates the anti-HNSCC of Feq(3). Feq(3) has potential as a cancer therapeutic agent against HNSCC.
關聯:	Phytomedicine, v.63, 153005
顯示於類別:	[化妝品應用與管理系(所)] 期刊論文

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