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

August-2018 Volume 53 Issue 2

Full Size Image

Cover Legend PDF

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

August-2018 Volume 53 Issue 2

Full Size Image

Cover Legend PDF

Article

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
View Affiliations / Copyright

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
Pages: 750-760
|
Published online on: May 11, 2018

https://doi.org/10.3892/ijo.2018.4402
Expand metrics +

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.

View Figures

View References

1	Liu X and Liu S, Chen J, He L, Meng X and Liu S: Baicalein suppresses the proliferation of acute T-lymphoblastic leukemia Jurkat cells by inhibiting the Wnt/β-catenin signaling. Ann Hematol. 95:1787–1793. 2016. View Article : Google Scholar : PubMed/NCBI
2	Han Z, Zhu S, Han X, Wang Z, Wu S and Zheng R: Baicalein inhibits hepatocellular carcinoma cells through suppressing the expression of CD24. Int Immunopharmacol. 29:416–422. 2015. View Article : Google Scholar : PubMed/NCBI
3	Chung H, Choi HS, Seo EK, Kang DH and Oh ES: Baicalin and baicalein inhibit transforming growth factor-β1-mediated epithelial-mesenchymal transition in human breast epithelial cells. Biochem Biophys Res Commun. 458:707–713. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wang XF, Zhou QM, Du J, Zhang H, Lu YY and Su SB: Baicalin suppresses migration, invasion and metastasis of breast cancer via p38MAPK signaling pathway. Anticancer Agents Med Chem. 13:923–931. 2013. View Article : Google Scholar : PubMed/NCBI
5	Ma X, Yan W, Dai Z, Gao X, Ma Y, Xu Q, Jiang J and Zhang S: Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. Drug Des Devel Ther. 10:1419–1441. 2016. View Article : Google Scholar :
6	Zhou QM, Wang S, Zhang H, Lu YY, Wang XF, Motoo Y and Su SB: The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells. Acta Pharmacol Sin. 30:1648–1658. 2009. View Article : Google Scholar : PubMed/NCBI
7	Kim HJ, Park C, Han MH, Hong SH, Kim GY, Hong SH, Kim ND and Choi YH: Baicalein induces caspase-dependent apoptosis associated with the generation of ROS and the activation of AMPK in human lung carcinoma A549 Cells. Drug Dev Res. 77:73–86. 2016. View Article : Google Scholar : PubMed/NCBI
8	Salcher S, Hagenbuchner J, Geiger K, Seiter MA, Rainer J, Kofler R, Hermann M, Kiechl-Kohlendorfer U, Ausserlechner MJ and Obexer P: C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma. Mol Cancer. 13:2242014. View Article : Google Scholar : PubMed/NCBI
9	Kuroda Y, Kuriyama H, Kihara S, Kishida K, Maeda N, Hibuse T, Nishizawa H, Matsuda M, Funahashi T and Shimomura I: Insulin-mediated regulation of decidual protein induced by progesterone (DEPP) in adipose tissue and liver. Horm Metab Res. 42:173–177. 2010. View Article : Google Scholar
10	Chen S, Gai J, Wang Y and Li H: FoxO regulates expression of decidual protein induced by progesterone (DEPP) in human endothelial cells. FEBS Lett. 585:1796–1800. 2011. View Article : Google Scholar : PubMed/NCBI
11	Sytnikova YA, Kubarenko AV, Schäfer A, Weber AN and Niehrs C: Gadd45a is an RNA binding protein and is localized in nuclear speckles. PLoS One. 6:e145002011. View Article : Google Scholar : PubMed/NCBI
12	Tong T, Ji J, Jin S, Li X, Fan W, Song Y, Wang M, Liu Z, Wu M and Zhan Q: Gadd45a expression induces Bim dissociation from the cytoskeleton and translocation to mitochondria. Mol Cell Biol. 25:4488–4500. 2005. View Article : Google Scholar : PubMed/NCBI
13	Tront JS, Hoffman B and Liebermann DA: Gadd45a suppresses Ras-driven mammary tumorigenesis by activation of c-Jun NH2-terminal kinase and p38 stress signaling resulting in apoptosis and senescence. Cancer Res. 66:8448–8454. 2006. View Article : Google Scholar : PubMed/NCBI
14	Yin F, Bruemmer D, Blaschke F, Hsueh WA, Law RE and Herle AJ: Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells. Oncogene. 23:4614–4623. 2004. View Article : Google Scholar : PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−∆ ∆ C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
16	Ye F, Wang H, Zhang L, Zou Y, Han H and Huang J: Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression. Tumour Biol. 36:4731–4740. 2015. View Article : Google Scholar : PubMed/NCBI
17	Watanabe H, Nonoguchi K, Sakurai T, Masuda T, Itoh K and Fujita J: A novel protein Depp, which is induced by progesterone in human endometrial stromal cells activates Elk-1 transcription factor. Mol Hum Reprod. 11:471–476. 2005. View Article : Google Scholar : PubMed/NCBI
18	Song L, Li J, Zhang D, Liu ZG, Ye J, Zhan Q, Shen HM, Whiteman M and Huang C: IKKbeta programs to turn on the GADD45α-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response. J Cell Biol. 175:607–617. 2006. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Related Articles