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In this study, we showed the ability of representative shogaol, which as a major component of ginger, to overcome TRAIL resistance by increasing apoptosis in colon cancer cells. Shogaol increased death receptor 5 (DR5) levels. Furthermore, shogaol decreased the expression level of antiapoptotic proteins (survivin and Bcl-2) and increased pro-apoptotic protein, Bax. Shogaol treatment induced apoptosis and a robust reduction in the levels of the antiapoptotic protein survivin but did not affect the levels of many other apoptosis regulators. Moreover, knockdown of survivin sensitized colon cancer cells to resistant of TRAIL-induced apoptosis. Therefore, we showed the functions of shogaol as a sensitizing agent to induce cell death of TRAIL-resistant colon cancer cells. This study gives rise to the possibility of applying shogaol as an antitumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant colon tumor therapy.

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