Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer

  • Authors:
    • Yuzo Maeda
    • Hiroki Takahashi
    • Nozomu Nakai
    • Takeshi Yanagita
    • Nanako Ando
    • Tomotaka Okubo
    • Kenta Saito
    • Kazuyoshi Shiga
    • Takahisa Hirokawa
    • Masayasu Hara
    • Hideyuki Ishiguro
    • Yoichi Matsuo
    • Shuji Takiguchi
  • View Affiliations

  • Published online on: March 7, 2018     https://doi.org/10.3892/ijo.2018.4308
  • Pages: 1661-1673
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Abstract

Apigenin is a natural flavonoid that exhibits anti-proliferative activity and induces apoptosis in various types of cancer, including colon cancer. The aim of the present study was to determine the mechanism underlying the apoptosis-inducing effect of apigenin in colon cancer. Apigenin reduced the proliferation of colon cancer cell lines, stimulated the cleavage of PARP and induced apoptosis in a dose-dependent manner. Apigenin treatment also suppressed the expression of the anti-apoptotic proteins Bcl-xL and Mcl-1. Small interfering RNA was used to knockdown Bcl-xL and Mcl-1 expression alone and in concert, and the proliferation and apoptosis of cancer cells were subsequently measured. The knockdown of Bcl-xL and Mcl-1 expression together markedly suppressed cell proliferation and induced apoptosis. Apigenin treatment also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which targets Bcl-xL and Mcl-1. The results of the current study therefore determined that apigenin induces the apoptosis of colon cancer cells by inhibiting the phosphorylation of STAT3 and consequently downregulates the anti-apoptotic proteins Bcl-xL and Mcl-1.
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May-2018
Volume 52 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Maeda Y, Takahashi H, Nakai N, Yanagita T, Ando N, Okubo T, Saito K, Shiga K, Hirokawa T, Hara M, Hara M, et al: Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer. Int J Oncol 52: 1661-1673, 2018
APA
Maeda, Y., Takahashi, H., Nakai, N., Yanagita, T., Ando, N., Okubo, T. ... Takiguchi, S. (2018). Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer. International Journal of Oncology, 52, 1661-1673. https://doi.org/10.3892/ijo.2018.4308
MLA
Maeda, Y., Takahashi, H., Nakai, N., Yanagita, T., Ando, N., Okubo, T., Saito, K., Shiga, K., Hirokawa, T., Hara, M., Ishiguro, H., Matsuo, Y., Takiguchi, S."Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer". International Journal of Oncology 52.5 (2018): 1661-1673.
Chicago
Maeda, Y., Takahashi, H., Nakai, N., Yanagita, T., Ando, N., Okubo, T., Saito, K., Shiga, K., Hirokawa, T., Hara, M., Ishiguro, H., Matsuo, Y., Takiguchi, S."Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer". International Journal of Oncology 52, no. 5 (2018): 1661-1673. https://doi.org/10.3892/ijo.2018.4308