Gastrodin destabilizes survivin and overcomes pemetrexed resistance

Jinzhuang Liao; Xiang Qing; Gaoyan Deng; Yeqing Xiao; Yaqian Fu; Shuangze Han; Xiaoying Li; Yu Gan; Wei Li

doi:10.1016/j.cellsig.2023.110851

Gastrodin destabilizes survivin and overcomes pemetrexed resistance

Cell Signal. 2023 Oct:110:110851. doi: 10.1016/j.cellsig.2023.110851. Epub 2023 Aug 14.

Authors

Jinzhuang Liao¹, Xiang Qing², Gaoyan Deng³, Yeqing Xiao⁴, Yaqian Fu⁵, Shuangze Han¹, Xiaoying Li¹, Yu Gan¹, Wei Li⁶

Affiliations

¹ Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
² Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
³ Department of Thoracic Surgery, Hunan Chest Hospital, Changsha, Hunan, China.
⁴ Department of Ultrasonography, Hunan Chest Hospital, Changsha, Hunan, China.
⁵ Xiangya Nursing School, Central South University, Changsha, Hunan, China.
⁶ Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: Weililx@csu.edu.cn.

PMID: 37586466
DOI: 10.1016/j.cellsig.2023.110851

Abstract

Survivin is a bifunctional protein that plays crucial roles in tumorigenesis. In the present study, we discovered that the natural product gastrodin suppressed the cell viability and colony formation of non-small cell lung cancer (NSCLC) cell lines A549, HCC827, and H460 in a dose-dependent manner. In addition, gastrodin enhanced the protein levels of cleaved-caspase 3 by activating the endogenous mitochondrial apoptosis pathway. Gastrodin inhibits protein kinase B (Akt)/WEE1/cyclin-dependent kinase 1 (CDK1) signaling to downregulate survivin Thr34 phosphorylation. Survivin Thr34 dephosphorylation caused by gastrodin interfered with the binding of ubiquitin-specific protease 19 (USP19), which eventually destabilized survivin. We revealed that the growth of NSCLC xenograft tumors was markedly suppressed by gastrodin in vivo. Furthermore, gastrodin overcomes pemetrexed resistance in vivo or in vitro. Our results suggest that gastrodin is a potential antitumor agent by reducing survivin in NSCLC.

Keywords: Gastrodin; Non-small cell lung cancer; Pemetrexed; Survivin; USP19.

Publication types

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

MeSH terms

Apoptosis
Carcinoma, Non-Small-Cell Lung* / metabolism
Cell Line, Tumor
Cell Proliferation
Endopeptidases
Humans
Lung Neoplasms* / metabolism
Pemetrexed / pharmacology
Survivin / metabolism

Substances

Survivin
Pemetrexed
gastrodin
USP19 protein, human
Endopeptidases