Dihydromyricetin Inhibited Migration and Invasion by Reducing S100A4 Expression through ERK1/2/β-Catenin Pathway in Human Cervical Cancer Cell Lines

Min-Chieh Hsin; Yi-Hsuan Hsiao; Pei-Ni Chen; Chiao-Wen Lin; Po-Hui Wang; Shun-Fa Yang; Chung-Yuan Lee

doi:10.3390/ijms232315106

Dihydromyricetin Inhibited Migration and Invasion by Reducing S100A4 Expression through ERK1/2/β-Catenin Pathway in Human Cervical Cancer Cell Lines

Int J Mol Sci. 2022 Dec 1;23(23):15106. doi: 10.3390/ijms232315106.

Authors

Min-Chieh Hsin^{1

2}, Yi-Hsuan Hsiao^{3

4

5}, Pei-Ni Chen^{1

6}, Chiao-Wen Lin^{7

8}, Po-Hui Wang^{1

9}, Shun-Fa Yang^{1

6}, Chung-Yuan Lee^{10

11}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
² National Institute of Cancer Research, National Health Research Institutes, Zhunan 350, Taiwan.
³ Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 500, Taiwan.
⁴ Women's Health Research Laboratory, Changhua Christian Hospital, Changhua 500, Taiwan.
⁵ School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
⁶ Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
⁷ Institute of Oral Sciences, Chung Shan Medical University, Taichung 402, Taiwan.
⁸ Department of Dentistry, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
⁹ Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
¹⁰ Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
¹¹ Department of Nursing, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi 613, Taiwan.

Abstract

Cervical cancer has a poor prognosis and is the fourth most common cancer among women. Dihydromyricetin (DHM), a flavonoid compound, exhibits several pharmacological activities, including anticancer effects; however, the effects of DHM on cervical cancer have received insufficient research attention. This study examined the antitumor activity and underlying mechanisms of DHM on human cervical cancer. Our results indicated that DHM inhibits migration and invasion in HeLa and SiHa cell lines. Mechanistically, RNA sequencing analysis revealed that DHM suppressed S100A4 mRNA expression in HeLa cells. Moreover, DHM inhibited the protein expressions of β-catenin and GSK3β through the regulated extracellular-signal-regulated kinase (ERK)1/2 signaling pathway. By using the ERK1/2 activator, T-BHQ, reverted β-catenin and S100A4 protein expression and cell migration, which were reduced in response to DHM. In conclusion, our study indicated that DHM inhibited cell migration by reducing the S100A4 expression through the ERK1/2/β-catenin pathway in human cervical cancer cell lines.

Keywords: DHM; S100A4; cervical cancer; metastasis; β-catenin.

MeSH terms

Cell Movement
Female
Flavonols* / pharmacology
HeLa Cells
Humans
MAP Kinase Signaling System
S100 Calcium-Binding Protein A4* / genetics
S100 Calcium-Binding Protein A4* / metabolism
Uterine Cervical Neoplasms* / drug therapy
Uterine Cervical Neoplasms* / genetics
beta Catenin* / metabolism

Substances

beta Catenin
S100 Calcium-Binding Protein A4
S100A4 protein, human
dihydromyricetin
Flavonols

Grants and funding

CSH-2022-E-002-Y3/Chung Shan Medical University Hospital