Curcumin Inhibits Invasiveness and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Through Reducing Matrix Metalloproteinase 2, 9 and Modulating p53-E-Cadherin Pathway

Abstract

Hypotheses. Epithelial-mesenchymal transition (EMT) and invasion play a critical role in cancer progression and metastasis. We have shown that low E-cadherin and high Twist expression are significantly correlated with prognostic survival prediction in oral squamous cell carcinoma (OSCC). This study aimed to determine the anti-invasive effect of curcumin on the expression of matrix metalloproteinases (MMPs) and of EMT regulators in OSCC. Methods. SCC-25 cells were treated with curcumin, and cell proliferation, invasion, and expression of MMPs and EMT regulators were assessed for cell viability by trypan blue exclusion, for invasion by Matrigel invasion chamber, and for EMT regulators and MMP changes in the levels of proteins by immunoblotting. Results. Our data showed that curcumin treatment not only decreased the expression of MMP-2 and MMP-9 to inhibit invasiveness in oral cancer but also modulated the expression of EMT markers, such as Snail, Twist, and E-cadherin, and induced p53 expression that is crucial to EMT repression. Conclusion. Curcumin has the potential to become an adjunctive regimen for the prevention of cancer progression and metastasis in oral cancer.

Treponema denticolaincreases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications

“…The effect of curcumin in decreasing MMP-2 and MMP-9 expression levels was reported in cancer cells, such as squamous cell carcinoma and osteoclastoma (Cao et al , 2015, Lee et al , 2015). Additionally, in vivo studies in humans and animals demonstrated curcumin’s effectiveness in decreasing the severity of periodontal diseases (Elburki et al , 2014, Nagasri et al , 2015, Bakir et al , 2016, Elburki et al , 2016).…”

Low Doses of Curcuma longa Modulates Cell Migration and Cell–Cell Adhesion

“…As higher doses of curcumin are related to impairment of the proliferation process of tumor cells (Lee et al, ), we analyzed the effects of lower doses of curcumin in normal and OSCC cell lines with different levels of differentiation and aggressiveness. We used keratinocytes (HACAT), high (CAL27) and low (SCC25) differentiated OSCCs, and fibroblast (NIH‐3T3), which were incubated with different doses of curcumin (2, 5, 10, 20, 30, 40, and 50 μM) for 24 h and then submitted to a proliferation assay (Fig.…”

“…The reported activity of curcumin against gastrointestinal cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, and lung cancer reflects its ability to affect multiple targets (Anand et al, ; Chen et al, ). Moreover, it has been found that curcumin inhibits oral cancer cell growth (Liao et al, ; Lee et al, ). However, these studies use variable curcumin concentrations (1–200 μM), and in most of them, the dosages used are usually higher than the ones that we used in this study.…”

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression

“…Among MMPs, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are vital enzymes involved in the degradation of gelatin, collagen and laminin, main components of ECM [9] and high expressions of them are indicators of high invasive potential of cancer cells and are related to poor prognosis of patients [3, 10, 11]. In contrast, down-regulation of MMP-2 and MMP-9 provides a preventive measure against tumor metastasis [12, 13]. Additionally, the 5′ end of promoter region of the MMP-2 and MMP-9 gene contains a variety of regulatory sequences that binds well-characterized transcriptional units of MMP-2 and MMP-9, including nuclear factor-kappa B (NF-κB), SP-1, cAMP response element-binding protein (CREB), and activator protein (AP)-1, possibly contributing to tumor metastasis [14, 15].…”