Phenethyl isothiocyanate suppresses EGF-stimulated SAS human oral squamous carcinoma cell invasion by targeting EGF receptor signaling

Abstract

Phenethyl isothiocyanate (PEITC) is a natural compound that is involved in chemoprevention as well as inhibition of cell growth and induction of apoptosis in several types of cancer cells. Previous studies have revealed that PEITC suppresses the invasion of AGS gastric and HT-29 colorectal cancer cells. However, the effects of PEITC on the metastasis of SAS oral cancer cells remain to be determined. Our results showed that PEITC treatment inhibited the invasion of EGF-stimulated SAS cells in a concentration-dependent manner, but appeared not to affect the cell viability. The expression and enzymatic activities of matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) were suppressed by PEITC. Concomitantly, we observed an increase in the protein expression of both tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2) in treated cells. Furthermore, PEITC treatments decreased the protein phosphorylation of epidermal growth factor receptor (EGFR) and downstream signaling proteins including PDK1, PI3K (p85), AKT, phosphorylated IKK and IκB to inactivate NF-κB for the suppression of MMP-2 and MMP-9 expression. In addition, PEITC can trigger the MAPK signaling pathway through the increase in phosphorylated p38, JNK and ERK in treated cells. Our data indicate that PEITC is able to inhibit the invasion of EGF-stimulated SAS oral cancer cells by targeting EGFR and its downstream signaling molecules and finally lead to the reduced expression and enzymatic activities of both MMP-2 and MMP-9. These results suggest that PEITC is promising for the therapy of oral cancer metastasis.

Mitogen-activated protein kinase signaling pathway in oral cancer (Review)

“…Certain inhibitors, including pterostilbene, astaxanthin and sulfasalazine (SSZ) (60)(61)(62), may also induce tumor cell apoptosis. Other inhibitors include those that have the potential to inhibit either oral tumor angiogenesis (for example, cetuximab) (63) or tumor invasion and metastasis (for example, vinculin, phenethyl isothiocyanate, cardiotoxin III and resveratrol) (64)(65)(66)(67). Their characteristics are listed in Table II. Besides the aforementioned inhibitors, it is worth noting that certain inhibitors may induce autophagic cell death via activation of the MAPK signaling pathway.…”

Matrix metalloproteinases in head and neck cancer: current perspectives

“…50 AP1 has been reported to increase the transcription of MMP9, 69,70 while EGFR and integrins enhance MMP9 activity. [71][72][73][74][75] Furthermore, MMP9 degrades type IV collagen and promotes HNSCC invasion. 76,77 Indeed, immunohistochemical studies correlated MMP expression with loss of type IV collagen α-chain areas in OSCC, and MMP9 has been proposed as an invasion-and infiltration-pattern marker of OSCC at the invasive front.…”

Maslinic acid activates mitochondria-dependent apoptotic pathway in cardiac carcinoma

“…Wu et al have shown that MA elicits apoptosis in salivary gland cancer cells by activating the Ca 2+ /p38 MAPK pathway [12]. Furthermore, some other compounds have also been reported to induce apoptosis in gastric cancers by activating the p38 MAPK pathway, such as calebin-A [13], and phenethyl isothiocyanate [14]. Although our studies showed that MA induces apoptosis by activating the p38 MAPK pathway, the possibility cannot be excluded that some other pathways may be also involved with the pro-apoptotic activity of MA.…”