• Life sciences · Jun 2013

    Multicenter Study

    The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.

    • Yun-Ju Chen, Hsin-Pao Chen, Yu-Jen Cheng, Yu-Heng Lin, Kuang-Wen Liu, Ming-Feng Hou, Yang-Chang Wu, Yi-Chen Lee, and Shyng-Shiou Yuan.
    • Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.
    • Life Sci. 2013 Jun 13; 92 (22): 1081-92.

    AimColorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells.Main MethodsThe anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays.Key FindingsData showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth.SignificanceWYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.Copyright © 2013 Elsevier Inc. All rights reserved.

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