Herbal formula Yangyinjiedu induces lung cancer cell apoptosis via activation of early growth response 1

Wenxiao Yang; Yani Kang; Qiang Zhao; Ling Bi; Lijing Jiao; Yunzhao Gu; Jun Lu; Jialin Yao; Di Zhou; Jielin Sun; Xiaodong Zhao; Ling Xu

doi:10.1111/jcmm.14501

Herbal formula Yangyinjiedu induces lung cancer cell apoptosis via activation of early growth response 1

J Cell Mol Med. 2019 Sep;23(9):6193-6202. doi: 10.1111/jcmm.14501. Epub 2019 Jun 25.

Authors

Wenxiao Yang¹, Yani Kang², Qiang Zhao², Ling Bi¹, Lijing Jiao^{1

3}, Yunzhao Gu², Jun Lu⁴, Jialin Yao¹, Di Zhou¹, Jielin Sun⁵, Xiaodong Zhao⁵, Ling Xu^{1

6}

Affiliations

¹ Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
³ Institute of Clinical Immunology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
⁶ Cancer Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Traditional Chinese Medicine (TCM) has been extensively used in clinical practices and proven to be effective against cancer. However, the underlying mechanisms remain to be investigated. In this study, we examined the anticancer activities of Chinese herbal formula Yangyinjiedu (YYJD) and found that YYJD exhibits cytotoxicity against lung cancer cells. Transcriptome analysis indicated that 2178 genes were differentially expressed (P < 0.05) upon YYJD treatment, with 1464 being (67.2%) up-regulated. Among these, we found that the tumour suppressor early growth response 1 (EGR1) is the most activated. We demonstrated that EGR1 contributes to YYJD-induced apoptosis in A549. Through dissecting EGR1-associated transcriptional network, we identified 275 genes as EGR1 direct targets, some targets are involved in apoptosis. Lastly, we observed that YYJD enhances EGR1 expression and induces cell death in tumour xenografts. Collectively, these findings suggest that YYJD exerts its anticancer activities through EGR1 activation, thus providing the evidence for its potential clinical application for lung cancer patients.

Keywords: ChIP-seq; EGR1; lung cancer; traditional Chinese medicine; transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects*
Drugs, Chinese Herbal / pharmacology*
Early Growth Response Protein 1 / genetics*
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Medicine, Chinese Traditional
Mice
Neoplasm Proteins / genetics
Transcriptome / drug effects
Transcriptome / genetics*
Xenograft Model Antitumor Assays

Substances

Drugs, Chinese Herbal
EGR1 protein, human
Early Growth Response Protein 1
Neoplasm Proteins