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5-aminolevulinic acid and sodium ferrous citrate decreased cell viability of gastric cancer cells by enhanced ROS generation through improving COX activity
Institution:1. Graduate School of Engineering, Faculty of Biomedical Engineering, Toin University of Yokohama, 1614, Kurogane-cho, Aoba-ku, Yokohama 225-8503, Japan;2. Department of Clinical Laboratory Medicine, Tokyo Women''s Medical University Hospital, 8-1, Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan;3. Department of Urology, Tokyo Women''s Medical University, 8-1, Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan;4. Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Taipei 10002, Taiwan;5. Department of Surgical Pathology, Tokyo Women''s Medical University, 8-1, Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan;1. Department of Neurosurgery and Endovascular Neurosurgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-Machi, Takatsuki, Osaka 569-8686, Japan;2. Department of Neurosurgery, Tanabe Neurosurgical Hospital, Fujiidera, Osaka, Japan;1. Thoracic Surgery Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan 33004, Taiwan, ROC;2. Pulmonology Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan 33004, Taiwan, ROC;3. Pathology Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan City 33004, Taiwan, ROC;4. Oncology Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan 33004, Taiwan, ROC;5. Radio-oncology Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan 33004, Taiwan, ROC;6. Radiology Department, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd. Taoyuan Dist., Taoyuan 33004, Taiwan, ROC
Abstract:BackgroundMitochondrial dysfunctions are related to cancer development.. 5-aminolevulinic acid (ALA) is used for photodynamic therapy (PDT). In this PDT, protoporphyrin IX (PpIX), which is converted from ALA, can generate reactive oxygen species (ROS) that kill the cancer cell. ALA is also reported to promote cytochrome c oxidase (COX) activity, which can generate ROS itself. Therefore, this study focused on the effect of ALA during PDT. In addition, in the previous study, sodium ferrous citrate (SFC) is reported to increase COX activity. So, this study also aims to improve the COX activity by the addition of SFC that can promote ROS generation, which has a cytotoxic effect.MethodsIn this study, we used ALA and SFC, then evaluated the effects of the treatment on the human gastric cancer cell line MKN45, including the induction of cell death.ResultsThis study showed that treatment with ALA and SFC increases intracellular heme and heme proteins. Moreover, COX activity was promoted, resulting in the production of intracellular reactive oxygen species (ROS), which eventually reduced the cell viability in human gastric cancer cell line MKN45.ConclusionOur study can detect ROS generation with ALA and SFC. Furthermore, we found this generation of ROS has a cytotoxic effect. Therefore, this phenomenon contributes to the effect of PDT.
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