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

Maeda,Yuzo; Takahashi,Hiroki; Nakai,Nozomu; Yanagita,Takeshi; Ando,Nanako; Okubo,Tomotaka; Saito,Kenta; Shiga,Kazuyoshi; Hirokawa,Takahisa; Hara,Masayasu; Ishiguro,Hideyuki; Matsuo,Yoichi; Takiguchi,Shuji

doi:10.3892/ijo.2018.4308

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
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Affiliations: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8602, Japan
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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