Resveratrol inhibited the metastatic behaviors of cisplatin‐resistant human oral cancer cells via phosphorylation of ERK/p‐38 and suppression of MMP‐2/9

• Published in: Journal of food biochemistry Vol. 45; no. 6; pp. e13666 - n/a
• Main Authors: Chang, Wen‐Shin, Tsai, Chia‐Wen, Yang, Jai‐Sing, Hsu, Yuan‐Man, Shih, Liang‐Chun, Chiu, Hong‐Yi, Bau, Da‐Tian, Tsai, Fuu‐Jen
• Format: Journal Article
• Language: English
• Published: United States 01.06.2021
• Subjects: cancer therapy; Carcinoma, Squamous Cell; Cell Line, Tumor; cisplatin; Cisplatin - pharmacology; cisplatin resistance; drug resistance; Humans; invasion; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; metastasis; migration; mouth neoplasms; Mouth Neoplasms - drug therapy; neoplasm cells; oral cancer; p38 Mitogen-Activated Protein Kinases; Phosphorylation; plant estrogens; resveratrol; Resveratrol - pharmacology; squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; migration; invasion; metastasis; resveratrol; cisplatin resistance; oral cancer
• ISSN: 0145-8884; 1745-4514; 1745-4514
• DOI: 10.1111/jfbc.13666

Cisplatin resistance is a major clinical problem in the clinical management of oral squamous cell carcinoma (OSCC) patients. Resveratrol is a natural phytoestrogen with antitumor activities. Whether resveratrol can overcome cisplatin resistance and prevent metastasis in OSCC cells is not known. In this study, we first examined the anti‐metastatic capacity of resveratrol and then explored the underlying mechanisms using a cisplatin‐resistant human OSCC cell line (CAR). The results demonstrated that at a non‐toxic dose range (25 to 75 µM), 24‐hr treatment of resveratrol was able to suppress the migration and invasion capacities of CAR cells dose dependently. Interestingly, 50 µM resveratrol treatment could significantly down‐regulate the expression of the phosphorylated forms of ERK and p‐38, in addition to those of MMP‐2 and MMP‐9. At the same time, the expression levels of phosphorylated ERK together with those unphosphorylated forms of ERK, p38, and JNK were all insignificantly altered. In conclusion, the signaling cascade for resveratrol's suppression of cisplatin‐resistant human oral cancer CAR cells was revealed and summarized. Also the rapid effectiveness in suppressing metastatic behaviors of drug‐resistant oral cancer cells of non‐toxic resveratrol might extend its application to the drug‐resistant oral cancer treatment in the near future. Practical applications Based on the evidence we provided in the study, we have proposed a model recording the possible pathway for resveratrol inhibiting the metastasis of cisplatin‐resistant oral cancer cells. We suppose this signaling pathway may work in other cancer cell lines, and can be helpful in full understanding of the drug‐resistance The current study provides the drug reposition evidence for resveratrol can inhibit the metastasis behaviors of cisplatin‐resistant oral cancer cells. This novel application is beneficial in not only clinical therapy for the oral cancer patients but also in translational medical science achievements.