Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-Snail signaling in breast cancer cells

Abstract

Epithelial-mesenchymal transition (EMT) is considered a critical event in cancer cell invasion and metastasis. Emerging evidence has shown that curcumin may prevent or delay the progression of cancer, an effect that may be partially due to its ability to disrupt EMT, yet this has not yet been demonstrated. In this study, we used lipopolysaccharide (LPS) to trigger EMT in MCF-7 and MDA-MB-231 breast cancer cell lines and showed that curcumin inhibited LPS-induced morphological changes, decreased the expression of LPS-induced markers of EMT such as vimentin, and increased the expression of E-cadherin, resulting in the inhibition of in vitro cell motility and invasiveness. We discovered that these actions were mediated through the inactivation of NF-κB-Snail signaling pathways. Our results indicate that curcumin plays an important role in the inhibition of LPS-induced EMT in breast cancer cells through the downregulation of NF-κB-Snail activity. These data provide a new perspective of the anti-invasive mechanism of curcumin, indicating that the effect is partly due to its ability to attack the EMT process.

LPS Upregulated VEGFR-3 Expression Promote Migration and Invasion in Colorectal Cancer via a Mechanism of Increased NF-κB Binding to the Promoter of VEGFR-3

“…The most very important signal pathway that LPS activates is NF-κB signal pathway. Huang T et al [13] reported that LPS promoted the progression of breast cancer cells though the NF-κB signal pathway. Zhao et al [30] revealed that LPS induced tumor angiogenesis also via NF-κB signaling.…”

“…Huang et al [12]reported that LPS induced the expression of MMPs increased the invasiveness of leukemia cells. And some studies also found that LPS could promote the epithelial-mesenchymal transition of tumor cells to enhance the cancer cells invasiveness [13,14]. However, LPS promote the specific mechanisms of progression of carcinoma is not entirely clear.…”

Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis

“…EMT in cancer cells involves loss of cell-cell junctions and the acquisition of cell motility and invasion factors. Multiple signaling pathways are closely associated with EMT in tumors, including TGFβ-Syk/Src-AKT/ERK, p38/JNK-ATF-2, PI3K/AKT, NF-κB and Wnt signaling pathways (2,30,(112)(113)(114). Additionally, IL-8 and its receptors have associations with EMT in cancer patients, thus blocking the IL-8/IL-8R axis may have be a potential strategy to improve prognosis for cancer patients.…”

Dietary Phytochemicals as Cancer Preventive Agents: Efficacy and Mechanisms

“…Moreover, curcumin has also been identified as an inhibitor of RTKs. Curcumin inhibits EGF-stimulated tyrosine phosphorylation of EGFR [6,[70][71][72] and decreases the activation of down-stream signaling in cell lines [6,[70][71][72]. A recent report has indicated that curcumin exhibits its anti-tumor effect by regulating miRNAs and the expressions of their target genes [73].…”

“…Numerous studies have reported that curcumin can inhibit NF-κB pathway in various cancer cells, including breast, ovary, prostate, colorectum, and pancreas [65][66][67][68][69]. Curcumin also inhibits the expressions of COX-2 and cyclin D1 [70,71]. Moreover, curcumin has also been identified as an inhibitor of RTKs.…”