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Inhibition of two gastric cancer cell lines induced by fucoxanthin involves downregulation of Mcl-1 and STAT3

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Abstract

Fucoxanthin is a natural carotenoid that had never been previously demonstrated to have anti-tumor effect on human gastric adenocarcinoma SGC-7901 or BGC-823 cells. Here it was found to inhibit proliferation and induce apoptosis through JAK/STAT signal pathway in these cells; the mechanism by which this occurred was investigated. We find that fucoxanthin significantly increased the number of apoptotic cells by propidium iodide (PI) dye staining and flow cytometry. Fucoxanthin (50 or 75 μM) induced SGC-7901 cells cycle arrest at S phase, while BGC-823 cells arrest at G2/M phase. RT-PCR and western blot analysis revealed that the expressions of Mcl-1, STAT3 and p-STAT3 were obviously decreased by fucoxanthin in a dose-dependent manner. Synthetic siRNA targeting Mcl-1 was transfected into cells which had no effect on expressions of STAT3. After pretreatment with AG490 (50 μM) which led to blocking of the JAK/STAT signal pathway, the reductive expressions of Mcl-1, STAT3 and p-STAT3 caused by fucoxanthin were inhibited. This is the first analysis of effects on SGC-7901 and BGC-823 cells by fucoxanthin. Fucoxanthin can induce cell-cycle arrest and apoptosis in these cells. These effects involved downregulation of Mcl-1, STAT3 and p-STAT3. This work is significant for better understanding of mechanisms leading to human gastric adenocarcinoma formation and informing exploitation of anti-tumor marine drug, and for providing Mcl-1 and STAT3 as potential therapeutic targets for gastric adenocarcinoma.

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Acknowledgements

This work was supported by West Light Foundation of The Chinese Academy of Sciences (2012 ~ 2016), the National Natural Science Foundation of China (No. 31101012), the Project from Qinghai Association for science and technology (2017KX05), and the International Cooperative Projects of Qinghai province (2017-HZ-811).

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Authors and Affiliations

  1. Pingdingshan University, Pingdingshan, 467000, China

    Rui-xue Yu

  2. Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, China

    Rui-tao Yu

  3. Qinghai Institute of Salt Lake, Chinese Academy of Sciences, Xining, 810008, China

    Zhong Liu

  4. Qinghai Key Laboratory of Tibetan Medicine, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, China

    Rui-tao Yu

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  1. Rui-xue Yu
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  2. Rui-tao Yu
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Correspondence to Rui-tao Yu or Zhong Liu.

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Yu, Rx., Yu, Rt. & Liu, Z. Inhibition of two gastric cancer cell lines induced by fucoxanthin involves downregulation of Mcl-1 and STAT3. Human Cell 31, 50–63 (2018). https://doi.org/10.1007/s13577-017-0188-4

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  • DOI: https://doi.org/10.1007/s13577-017-0188-4

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