Antitumor effect of kurarinone and underlying mechanism in small cell lung carcinoma cells

doi:10.2147/OTT.S214964

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標題:	Antitumor effect of kurarinone and underlying mechanism in small cell lung carcinoma cells
作者:	Chung, Ting-Wen Lin, Chi-Chien Lin, Shih-Chao Chan, Hong-Lin Ching-Chieh Yang(楊清傑)
貢獻者:	Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol Natl Tsing Hua Univ, Dept Med Sci Natl Chung Hsing Univ, Inst Biomed Sci China Med Univ Hosp, Dept Med Res George Mason Univ, Natl Ctr Biodef & Infect Dis, Sch Syst Biol Chi Mei Med Ctr, Dept Radiat Oncol Chia Nan Univ Pharm & Sci, Dept Pharm
關鍵字:	kurarinone small cell lung carcinoma apoptosis caspase migration invasiveness
日期:	2019
上傳時間:	2020-07-29 13:51:55 (UTC+8)
出版者:	DOVE MEDICAL PRESS LTD
摘要:	Background: Kurarinone, a prenylated flavonone isolated from the roots of Sophora flavescens, is known to be cytotoxic against many human cancer cells but not human small cell lung carcinoma (SCLC) yet. Also, the exact molecular mechanism of kurarinone for induction cytotoxicity remains unknown. Material and methods: We investigated the effects of kurarinone on cell proliferation, apoptosis, and migration in H1688 SCLC cells. Cell viability was determined by the MTT assay. Apoptotic indices such as cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptors were evaluated by flow cytometry. Transwell migration and invasion assays were also included. Results: Our results indicated that kurarinone significantly decreased H1688 cell viability and induced the accumulation of sub-G1 fractions by activating caspase-3, -9, and PARP cleavage accompanied by the elevated release of cytochrome c and mitochondrial dysfunction in H1688 cells. Additionally, kurarinone promoted Fas and TRAIL receptor-1 and -2 expression via the caspase-8/Bid pathway, suggesting that kurarinone triggered apoptosis via the mitochondria-mediated and receptor-mediated apoptotic pathways. We also observed that kurarinone repressed migration and invasion capabilities of SCLC cells by suppressing the expression of epithelial-mesenchymal transition-related proteins and matrix metalloproteinases. Conclusion: Our findings provided evidence that kurarinone can induce apoptosis in SCLC cells via multiple mechanisms and delayed the cell migration and invasion of SCLC cells.
關聯:	Oncotargets and the rapy, v.12, pp. 6119-6131
显示于类别:	[藥學系(所)] 期刊論文

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