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Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo.

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机构： [1]Department of Surgery and Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan [2]Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam [3]Division of Colorectal Surgery, Taichung Veterans General Hospital, Taichung, Taiwan [4]Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan [5]Mackay Medicine, Nursing and Management College, Taipei, Taiwan [6]Department of Chinese Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan [7]Department of Nursing, MeiHo University, Pingtung, Taiwan [8]Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan [9]Department of Biotechnology, Bharathiar University, Coimbatore, India [10]Division of Chest Medicine, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan [11]Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan [12]Department of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China [13]Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

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关键词： AKT CPT11 resistance fisetin IGF1R Oxaliplatin resistance PI3 K

摘要：

Irinotecan (CPT11) and Oxaliplatin have been used in combination with fluorouracil and leucovorin for treating colorectal cancer. However, the efficacy of these drugs is reduced due to various side effects and drug resistance. Fisetin, a hydroxyflavone possess anti-proliferative, anti-cancer, anti-inflammatory, and antioxidant activity against various types of cancers. Apart from that, fisetin has been shown to induce cytotoxic effects when combined with other known chemotherapeutic drugs. In this study, we aimed to investigate whether Fisetin was capable of sensitizing both Irinotecan and Oxaliplatin resistance colon cancer cells and explored the possible signaling pathways involved using In vitro and In vivo models. The results showed that Fisetin treatment effectively inhibited cell viability and apoptosis of CPT11-LoVo cells than Oxaliplatin (OR) and parental LoVo cancer cells. Western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase-8, and Cytochrome-C expressions possibly by inhibiting aberrant activation of IGF1R and AKT proteins. Furthermore, fisetin inhibited tumor growth in athymic nude mouse xenograft model. Overall, our results provided a basis for Fisetin as a promising agent to treat parental as well as chemoresistance colon cancer. © 2018 Wiley Periodicals, Inc.

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出版当年[2017]版：

大类 | 2 区生物

小类 | 2 区生理学 3 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 3 区细胞生物学 3 区生理学

第一作者：

第一作者机构： [1]Department of Surgery and Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan

通讯作者：

通讯机构： [11]Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan [12]Department of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China [13]Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan [*1]Graduate Institute of Basic Medical Science, School of Medicine, China Medical University and Hospital, 91 Hsueh-Shih Road, Taichung 404, R.O.C. Taiwan.

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Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo.

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