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

Abstract

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

Comparative Effects of Boric Acid and Resveratrol on McF-7 Breast Cancer Cells Metastatic Behaviour

“…It has been observed in our study that the MMP-9 immunoreactivities of RES and CONT groups were similar (p = 0,181). In the year of 2021, Chang et al (2021) have reported that applying 50 µM of Resveratrol for 24 hours causes a significant decrease in the MMP-9 expression of cancer cells Chang et al (2021). Likewise, in the year of 2016, Park et al, have shown that there was a significant decrease in the MMP-9 expressions of breast cancer cells when treated with 10 µM of resveratrol, that were loaded to pieces of gold, for 24 hours Park et al (2016).…”

“…Chen et al (2019) and Xu et al (2017) have shown in their in vitro studies that in breast cancer and gastric cancer cells, resveratrol changes protein expressions that play a role in mesenchymal transition such as E-Cadherin and Vimentin Chen et al (2019), Xu et al (2017). Likewise, in the year of 2021, Chang et al, (2021) have reported that the application of 50 µM Resveratrol decreases the expression of MMP-9 protein in cancer cells Chang et al (2021). Boron, a trace element for organisms, has high affinity to oxygen and nature is filled with plenty of borates such as in the forms of boric acid and borax Devirian and Volpe (2003) .…”

Protective Effects of Crocetin on Arsenic Trioxide-induced Oxidative Stress in Human Umbilical Vein Endothelial Cells

“…Measurement of cell apoptosis. Cell apoptosis of HUVEC cells was examined as previously published (26,27). After drug treatments, HUVEC cells were ethanol-fixed and incubated with propidium iodide buffer for 30 min in the dark at 37˚C.…”

“…Intracellular ROS production. Intracellular ROS production was measured as previously described (26,27). After drug treatments, HUVEC cells were harvested, re-suspended in 10 μM DCFH-DA, incubated at 37˚C for 30 min, and analyzed by flow cytometry (BD Biosciences).…”

Molecular Basis of Resveratrol-Induced Resensitization of Acquired Drug-Resistant Cancer Cells

“…Prevention of EMT-like characteristics by RES has also been observed in CIS-resistant cancer cells. RES reduced the migration and invasive capacity of CIS-resistant CAR cells by inhibiting the phosphorylation of ERK and p-38MAPK as well as suppressing MMP2 and MMP9 expression [ 79 ]. Likewise, RES reversed CIS-induced snail expression by blocking the ERK pathway, thereby inhibiting the morphological changes and cell migration in ovarian cancer A2780 and A2780CP (resistant to CIS) cells [ 71 ].…”