Ugonin P inhibits lung cancer motility by suppressing DPP-4 expression via promoting the synthesis of miR-130b-5p

Chih-Ying Wu; Shubham Suresh Ghule; Chih-Chuang Liaw; David Achudhan; Shuen-Yih Fang; Po-I Liu; Chang-Lun Huang; Ching-Liang Hsieh; Chih-Hsin Tang

doi:10.1016/j.biopha.2023.115483

Ugonin P inhibits lung cancer motility by suppressing DPP-4 expression via promoting the synthesis of miR-130b-5p

Biomed Pharmacother. 2023 Nov:167:115483. doi: 10.1016/j.biopha.2023.115483. Epub 2023 Sep 12.

Authors

Chih-Ying Wu¹, Shubham Suresh Ghule², Chih-Chuang Liaw³, David Achudhan⁴, Shuen-Yih Fang⁵, Po-I Liu⁶, Chang-Lun Huang⁷, Ching-Liang Hsieh⁸, Chih-Hsin Tang⁹

Affiliations

¹ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; Department of Neurosurgery, China Medical University Hsinchu Hospital, Hsinchu, Taiwan.
² International Master Program of Biomedical Sciences, China Medical University, Taichung, Taiwan.
³ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan; Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
⁵ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁶ Department of Physical Therapy, Asia University, Taichung, Taiwan; Department of General Thoracic Surgery, Asia University Hospital, Taichung, Taiwan.
⁷ Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, Division of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
⁸ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, Taiwan. Electronic address: clhsieh@mail.cmuh.org.tw.
⁹ International Master Program of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan. Electronic address: chtang@mail.cmu.edu.tw.

PMID: 37703658
DOI: 10.1016/j.biopha.2023.115483

Abstract

Lung cancer is the leading cause of cancer-related death worldwide, and the survival rate of metastatic lung cancer is exceedingly low. Helminthostatchys Zeylanica (H. Zeylanica) is a Chinese herbal medicine renowned for its anti-inflammatory, immunomodulatory, and anti-cancer activities in various cellular and animal studies. The current study evaluated the effects of H. Zeylanica derivatives on lung cancer cells. We determined that dipeptidyl peptidase-4 (DPP-4) expression levels were higher in lung cancer tissues than in normal tissues. We also determined that DPP-4 expression levels were higher in the metastatic stage and strongly correlated with lung cancer survival rates. An H. Zeylanica derivative (ugonin P) was shown to inhibit DPP-4 mRNA and protein expression in two lung cancer cell lines in a dose-dependent manner. Ugonin P was shown to decrease migration and invasion activities in lung cancer cells while promoting the synthesis of miR-130b-5p, which was found to negatively regulate DPP-4 protein expression and cell motility in lung cancer. We determined that ugonin P suppresses the DPP-4-dependent migration and invasion of lung cancer cells by downregulating the RAF/MEK/ERK signalling pathway and enhancing the expression of miR-130b-5p. This study provides compelling evidence that ugonin P could be used to develop novel therapeutic agents for the treatment of lung cancer.

Keywords: DPP-4; Helminthostatchys Zeylanica; Lung cancer; Ugonin P; miR-130b-5p.