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

Ting-Wen Chung,*,1 Chi-Chien Lin,2,3,* Shih-Chao Lin,4 Hong-Lin Chan,1 Ching-Chieh Yang5,61Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu 300, Taiwan; 2Institute of Biomedical Science, National Chung‑hsing University, Taichung 402, Taiwan; 3Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; 4National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, USA; 5Department of Radiation Oncology, Chi-Mei Medical Center, Tainan 710, Taiwan; 6Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan*These authors contributed equally to this workBackground: 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.Keywords: kurarinone, small cell lung carcinoma, apoptosis, caspase, migration, invasiveness