Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

Abstract

Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma

“…Since the Mitogen-activated protein kinases (MAPK) are involved in regulating MMP-2, which is known as a metastasis pathway [ 23 , 24 ], the effects of morusin on the expressions of MAPK pathway were investigated by Western blotting assay. The results demonstrate that morusin significantly inhibited the phosphorylation of FAK, Src, and ERK1/2 in the NPC-39 cell lines, while no effect on the phosphorylation of AKT, p38, and JNK1/2 was measured ( Figure 5 A,B).…”

Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase‐2/9 and epithelial‐mesenchymal transition

“…When natural products affect cancer cells at high concentrations, this can be explained by their potency to induce apoptosis 21 . However, low cytotoxic concentrations of compounds are commonly chosen for migration studies 38–40 . As for POMx, at low cytotoxic concentrations it also shows wound healing inhibition in breast cancer stem cells 16 .…”

Carbonic Anhydrase III Promotes Cell Migration and Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinoma

“…OSCC metastasis can be regulated though many signaling pathways, such as MAPK, PI3 K/AKT, and FAK/Src [35][36][37]46,47]. Our results showed that the cell migration ability was increased in CA III overexpression cell lines and decreased after FAK inhibitor treatment (Figure 4 C).…”

“…Numerous studies have speculated that the FAK/Src pathway participates in oral cancer migration [34][35][36][37]. Therefore, we also determined whether CA III could regulate the EMT and migration ability though Src and FAK signaling pathways.…”