Pinosylvin reduced migration and invasion of oral cancer carcinoma by regulating matrix metalloproteinase-2 expression and extracellular signal-regulated kinase pathway

Mu-Kuan Chen; Yen-Tze Liu; Jen-Tsun Lin; Chia-Chieh Lin; Yi-Ching Chuang; Yu-Sheng Lo; Yi-Ting Hsi; Ming-Ju Hsieh

doi:10.1016/j.biopha.2019.109160

Pinosylvin reduced migration and invasion of oral cancer carcinoma by regulating matrix metalloproteinase-2 expression and extracellular signal-regulated kinase pathway

Biomed Pharmacother. 2019 Sep:117:109160. doi: 10.1016/j.biopha.2019.109160. Epub 2019 Jul 1.

Authors

Mu-Kuan Chen¹, Yen-Tze Liu², Jen-Tsun Lin³, Chia-Chieh Lin⁴, Yi-Ching Chuang⁴, Yu-Sheng Lo⁴, Yi-Ting Hsi⁴, Ming-Ju Hsieh⁵

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
² Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan.
³ Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
⁴ Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
⁵ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan; Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan. Electronic address: 170780@csmu.edu.tw.

PMID: 31387166
DOI: 10.1016/j.biopha.2019.109160

Abstract

Background: Pinosylvin possesses several biological properties, including anti-inflammatory, antitumor, and antioxidant characteristics. However, the effects of pinosylvin on the migration and invasion of human oral cancer cells and the underlying mechanisms remain unclear.

Hypothesis/purpose: In this research, we investigated the outcome of different concentrations of pinosylvin (0-80 μM) on the metastatic and invasive abilities of SAS, SCC-9, and HSC-3 cells.

Methods and results: Western blotting assay and Gelatin zymography assay indicated that pinosylvin inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and reduced its protein level but increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). Additionally, the wound healing assay and Transwell method showed that pinosylvin reduced the migration of SAS, SCC-9 and HSC-3 oral cancer cells. Besides, pinosylvin decreased the phosphorylation of ERK1/2 protein experssion in both SAS and SCC-9 cells.

Conclusion: These results indicate that pinosylvin is a potential anticancer agent for preventing oral cancer metastasis.

Keywords: MMP-2; Migration; Oral squamous cell carcinoma; Pinosylvin; TIMP-2.

MeSH terms

Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / metabolism
Cell Line, Tumor
Cell Movement / drug effects*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Humans
MAP Kinase Signaling System / drug effects
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase Inhibitors / pharmacology
Mouth Neoplasms / drug therapy*
Mouth Neoplasms / metabolism
Neoplasm Invasiveness / pathology*
Phosphorylation / drug effects
Signal Transduction / drug effects
Stilbenes / pharmacology*
Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

Matrix Metalloproteinase Inhibitors
Stilbenes
Tissue Inhibitor of Metalloproteinase-2
pinosylvin
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 2