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Kurarinone Synergizes TRAIL-Induced Apoptosis in Gastric Cancer Cells

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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been identified as a promising anti-tumor agent against in a variety of cancers. However, gastric cancer cells are less sensitive than other cancer cells to TRAIL-induced apoptosis. Here, we combined TRAIL with kurarinone, a natural compound, to induce apoptosis in gastric cancer cell lines SGC7901. After the cells were treated with TRAIL and/or kurarinone, the cell viability and apoptosis were examined by MTT and flow cytometry, respectively. The expression of apoptosis-associated proteins was determined by western blot and q-RT-PCR. Kurarinone at low concentration significantly potentiated the cytotoxic effect of TRAIL by enhancing apoptosis as well as cell cycle arrest at G2/Mphase. The enhancement of apoptosis TRAIL induced by kurarinone involved downregulation of anti-apoptotic proteins Mcl-1 and c-FLIP as well as inhibition of STAT3 signaling. Moreover, we found that STAT3 inhibitor could synergistically enhanced TRAIL-induced apoptosis, similar to kurarinone. Kurarinone synergizes TRAIL-induced apoptosis in human gastric cancer cells. The synergistic effect between these two drugs is associated with downregulation of Mcl-1 and c-FLIP via inhibiting STAT3 signaling. The combination of TRAIL and kurarinone might be an effective regimen for the treatment of advanced gastric cancer.

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Authors and Affiliations

  1. Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Wenchao Zhou & Dazheng Wu

  2. Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China

    Wenchao Zhou, Aili Cao & Li Wang

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  1. Wenchao Zhou
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  2. Aili Cao
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  3. Li Wang
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  4. Dazheng Wu
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Correspondence to Dazheng Wu.

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Zhou, W., Cao, A., Wang, L. et al. Kurarinone Synergizes TRAIL-Induced Apoptosis in Gastric Cancer Cells. Cell Biochem Biophys 72, 241–249 (2015). https://doi.org/10.1007/s12013-014-0444-0

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