Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs
| Autor: | Y.H. Zhou, Hong Yang, Jie Dou, Xuan Rao, Meng-Qi Su, Xin‑Hao Zhuang, Guangyong Peng, Changlin Zhou, Xue-Jia Ke, Baiyong Shen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival MAP Kinase Signaling System p38 mitogen-activated protein kinases Cell Cycle Proteins Biology 03 medical and health sciences chemistry.chemical_compound Annexin Cell Line Tumor Humans Phosphorylation Protein kinase A Cell Proliferation A549 cell Kinase Intracellular Signaling Peptides and Proteins Nuclear Proteins Proteins HCT116 Cells Baicalein Cell biology Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology Oncology chemistry Apoptosis A549 Cells Colonic Neoplasms Flavanones GADD45A |
| Zdroj: | International journal of oncology. 53(2) |
| ISSN: | 1791-2423 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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