Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo. Issue 9 (25th March 2018)

• Record Type: Journal Article
• Authors: Jeng, Long‐Bin; Kumar Velmurugan, Bharath; Chen, Ming‐Cheng; Hsu, Hsi‐Hsien; Ho, Tsung‐Jung; Day, Cecilia‐Hsuan; Lin, Yueh‐Min; Padma, V. Vijaya; Tu, Chuan‐Chou; Huang, Chih‐Yang
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 9(2018:Sep.)
• Page Start: 7134
• Page End: 7142
• Publication Date: 2018-03-25
• Subjects: AKT -- CPT11 resistance -- fisetin -- IGF1R -- Oxaliplatin resistance -- PI3 K; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26532
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : 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. Abstract : Present study investigated whether Fisetin is capable of sensitizing both Irinotecan and Oxaliplatin resistance colon cancer cells and explored its possible signaling pathways involved using in vitro and in vivo models.