Bigelovin triggered apoptosis in colorectal cancer in vitro and in vivo via upregulating death receptor 5 and reactive oxidative species
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摘要Colorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that bigelovin has potential to be developed as therapeutic agent for CRC patients.
著者Li MY, Song LH, Yue GGL, Lee JKM, Zhao LM, Li L, Zhou XN, Tsui SKW, Ng SSM, Fung KP, Tan NH, Lau CBS
期刊名稱Scientific Reports
詳細描述Article number: 42176
出版年份2017
月份2
日期9
卷號7
出版社NATURE PUBLISHING GROUP
國際標準期刊號2045-2322
電子國際標準期刊號2045-2322
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences;Science & Technology - Other Topics

上次更新時間 2020-11-09 於 02:51