Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs

Su,Meng-Qi; Zhou,Yi-Ran; Rao,Xuan; Yang,Hong; Zhuang,Xin‑Hao; Ke,Xue-Jia; Peng,Guang-Yong; Zhou,Chang-Lin; Shen,Bai-Yong; Dou,Jie

doi:10.3892/ijo.2018.4402

Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs

Authors:
- Meng-Qi Su
- Yi-Ran Zhou
- Xuan Rao
- Hong Yang
- Xin‑Hao Zhuang
- Xue-Jia Ke
- Guang-Yong Peng
- Chang-Lin Zhou
- Bai-Yong Shen
- Jie Dou
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Affiliations: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210029, P.R. China, Department of General Surgery, Ruijin Hospital, Research Institute of Pancreatic Diseases, School of Medicine, Shanghai JiaoTong University, Shanghai 200025, P.R. China, Department of Chemistry and Biochemistry, University of Oregon, OR 97401, USA, Division of Infectious Diseases, Allergy and Immunology and Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA
Published online on: May 11, 2018 https://doi.org/10.3892/ijo.2018.4402
Pages: 750-760

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Abstract

Baicalein has efficient antitumor properties and has been reported to promote the apoptosis of several human cancer cell lines. Decidual protein induced by progesterone (DEPP), a transcriptional target of Forkhead Box O, was originally identified from the human endometrial stromal cell cDNA library. However, the expression and physiological functions of DEPP in human colon cancer cells remain to be fully elucidated. In the present study, it was reported that baicalein stimulated apoptosis and morphological changes of HCT116, A549 and Panc‑1 cells in a dose-dependent manner. It also upregulated the mRNA and protein levels of DEPP and growth arrest and DNA damage-inducible 45α (Gadd45a). In addition, the overexpression of DEPP promoted mitogen-activated protein kinase (MAPK) phosphorylation. To further investigate the role of DEPP and Gadd45a in baicalein-induced apoptosis, HCT116 cells were transfected with small interfering RNA against either DEPP or Gadd45a as in vitro models. Through an Annexin V/PI double staining assay, it was observed that baicalein-induced apoptosis was impaired by the inactivation of either DEPP or Gadd45a, which in turn restricted the baicalein-induced activation of caspase‑3 and caspase‑9 and phosphorylation of MAPKs. In addition, the inhibition of c‑Jun N‑terminal kinase (JNK)/p38 activity with SP600125/SB203580 decreased the expression of Gadd45a, whereas the inactivation of extracellular signal-regulated kinase with SCH772984 had no effect on the expression of Gadd45a. Taken together, these results demonstrated that baicalein induced the upregulation of DEPP and Gadd45a, which promoted the activation of MAPKs with a positive feedback loop between Gadd45a and JNK/p38, resulting in a marked apoptotic response in human colon cancer cells. These results indicated that baicalein is a potential antitumor drug for the treatment of colon cancer.

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