Triptolide prevents proliferation and migration of Esophageal Squamous Cell Cancer via MAPK/ERK signaling pathway

Ma Yanchun; Wang Yi; Wang Lu; Qian Yu; Yang Jian; Kong Pengzhou; Yan Ting; Li Hongyi; Wang Fang; Cheng Xiaolong; Cui Yongping

doi:10.1016/j.ejphar.2019.02.030

Triptolide prevents proliferation and migration of Esophageal Squamous Cell Cancer via MAPK/ERK signaling pathway

Eur J Pharmacol. 2019 May 15:851:43-51. doi: 10.1016/j.ejphar.2019.02.030. Epub 2019 Feb 16.

Authors

Ma Yanchun¹, Wang Yi¹, Wang Lu¹, Qian Yu¹, Yang Jian¹, Kong Pengzhou¹, Yan Ting¹, Li Hongyi¹, Wang Fang¹, Cheng Xiaolong¹, Cui Yongping²

Affiliations

¹ Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
² Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: cuiyp@sxmu.edu.cn.

PMID: 30779917
DOI: 10.1016/j.ejphar.2019.02.030

Abstract

Triptolide, the component of traditional Chinese herb, has been used as an inflammatory medicine and reported to be anti-tumor for various cancers recently. However, the effect of triptolide on Esophageal Squamous Cell Cancer (ESCC) has not yet been elucidated. In the study, we found that triptolide significantly inhibited cell proliferation, invasion, migration and survivability of ESCC cells. Moreover, we observed that triptolide induced ESCC cell cycle arrest at the G1/S phase and apoptosis through cyclin D1-CDK4/6 regulation and caspases activation. In addition, we revealed that triptolide regulates cell apoptosis and metastasis by p53 and mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, respectively. Meanwhile, the inhibitory effect of triptolide on ESCC was validated in mouse xenograft model. So, we propose that triptolide may be a candidate drug for ESCC.

Keywords: ESCC; MAPK/ERK pathway; Metastasis; Proliferation; Triptolide.

MeSH terms

Animals
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Movement / drug effects*
Cell Proliferation / drug effects
Diterpenes / pharmacology*
Epoxy Compounds / pharmacology
Esophageal Neoplasms / pathology*
Esophageal Squamous Cell Carcinoma / pathology*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Humans
MAP Kinase Signaling System / drug effects*
Mice
Mitogen-Activated Protein Kinases / metabolism*
Neoplasm Metastasis
Phenanthrenes / pharmacology*
Xenograft Model Antitumor Assays

Substances

Diterpenes
Epoxy Compounds
Phenanthrenes
triptolide
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases