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Int. J. Mol. Sci. 2017, 18(7), 1508; doi:10.3390/ijms18071508

Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation

Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan
Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan
Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan
Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
Department of Pharmacy, College of Pharmacy & Health Care, Tajen University, Pingtung 90741, Taiwan
Center for Drug Abuse and Addiction, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan
Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi61363, Taiwan
Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin 63862, Taiwan
Department of Respiratory Care, Chang Gung University of Science and Technology, Chia-Yi Campus, Chia-Yi 61363, Taiwan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 14 June 2017 / Revised: 4 July 2017 / Accepted: 6 July 2017 / Published: 13 July 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma. View Full-Text
Keywords: cudraflavone C; mitochondria; melanoma cells; MAPKs; pro-oxidation; apoptosis cudraflavone C; mitochondria; melanoma cells; MAPKs; pro-oxidation; apoptosis

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lee, C.-W.; Yen, F.-L.; Ko, H.-H.; Li, S.-Y.; Chiang, Y.-C.; Lee, M.-H.; Tsai, M.-H.; Hsu, L.-F. Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation. Int. J. Mol. Sci. 2017, 18, 1508.

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