http://scholars.ntou.edu.tw/handle/123456789/5895
標題: | Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression | 作者: | Chen, Li-Mei Liu, Po-Yen Chen, Yen-An Tseng, Hong-Yu Shen, Pei-Chun Hwang, Pai-An Hsu, Hsin-Ling |
關鍵字: | MOLECULAR-WEIGHT FUCOIDAN;IN-VITRO;SULFATED POLYSACCHARIDES;MESENCHYMAL TRANSITION;CYTOKINE PRODUCTION;DRUG-RESISTANCE;CANCER;GROWTH;CARCINOMA;PATHWAY | 公開日期: | 19-九月-2017 | 出版社: | NATURE PORTFOLIO | 卷: | 7 | 來源出版物: | SCI REP-UK | 摘要: | Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53(+/+)) or without (p53(-/-)) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks. Subsequent administration of Oligo-Fucoidan to etoposide-treated cells promotes p53 accumulation, p21 expression and significant decreases in ataxia-telangiectasia- mutated (ATM), checkpoint kinase 1 (Chk1) and gamma-H2AX phosphorylation in p53(+/+) cells compared with p53(-/-)cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and gamma-H2AX phosphorylation, particularly in the presence of p53. Furthermore, Oligo-Fucoidan supplementation increases cancer cell death and attenuates the adverse effects induced by etoposide that decreases production of the pro-inflammatory cytokine IL-6 and chemokine CCL2/MCP-1. Importantly, Oligo-Fucoidan decreases the tumor-promoting M2 macrophages in microenvironment as well as collaborates with p53 and works in combination with etoposide to prevent HCT116 tumorigenicity. Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment. |
URI: | http://scholars.ntou.edu.tw/handle/123456789/5895 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-017-12111-1 |
顯示於: | 生命科學暨生物科技學系 03 GOOD HEALTH AND WELL-BEING |
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