Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells

Zhao

et al. 2020

OTT

Self Cite

Background: So far, little research has been conducted regarding the underlying mechanism of renal carcinogenesis at molecular level. Epithelial-mesenchymal transition (EMT) exerts an important part during tumor genesis as well as the development through mitogen-activated protein kinase (MAPK) pathways. Therefore, we hypothesized that EMT could promote renal cell carcinoma (RCC) progression via the ERK5/AP-1pathway. Materials and Methods: The RCC cell lines were utilized to be the models with in vitro exposure to cigarette smoke extract (CSE). We used the curcumin for the EMT intervention study. In the present study, immunohistochemistry (IHC), Western blotting, and real-time quantitative reverse transcription PCR had been used to determine the experimental results. EMT phenotypic alterations were assessed by changes in cell morphology, invasion and transfer ability, as well as expression of epithelial and mesenchymal markers. Results: In human renal cell carcinoma tissue, E-cadherin expression within the smoking renal cancer patients was down-regulated compared with that among the non-smokers. However, Vimentin, N-cadherin, and TWIST levels increased (P<0.05). Significantly, we clarified that ERK5/AP-1 exerted positive regulation on the renal cell carcinoma EMT mediated by CS, which was suggested based on the results of CS activating the ERK5/AP-1 pathway, as well as ERK5 inhibition via XMD8-92 reversed AP-1 protein levels and the EMT process. Furthermore, curcumin showed the same inhibitory effect as XMD8-92 and significantly reversed CSinduced EMT through inhibiting the ERK5/AP-1 signaling pathway. Conclusion: The above results indicated that ERK5/AP-1 signaling pathway exerts a vital part for CS-associated RCC development and cancer intervention.

Section: Dovepressmentioning

confidence: 99%

<p>Curcumin Negatively Regulates Cigarette Smoke-Induced Renal Cell Carcinoma Epithelial–Mesenchymal Transition Through the ERK5/AP-1 Pathway</p>

Zhao

et al. 2020

OTT

Self Cite

“…The ethanol extract of S. chinensis has been reported to suppress streptozotocin-induced EMT in diabetic nephropathy mice by enhancing E-cadherin expression (Zhang et al, 2012). In general, effect of natural products on the metastatic abilities of cancer cells is determined using non-cytotoxic concentration at proper time course (Liu et al, 2017; Kim et al, 2018). In the present study, effects of G.A on EMT, migration, and invasion of CRC cells were determined using lower concentration of 20 uM, which did not significantly decrease the cell viability of CRC cells after G.A treatment for 24 h. The expression level of the epithelial marker E-cadherin concentration-dependently increased, whereas that of the mesenchymal marker N-cadherin and vimentin were decreased by G.A treatment.…”

Section: Discussionmentioning

confidence: 99%

Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells

et al. 2018

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial–mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC.

“…And curcumin could inhibit Fra-1/AP-1-mediated gene expression by inhibiting the binding of AP-1 to its cognate motif 92. Liu et al93 also found that curcumin could effectively reduce the low concentration of benzidine-induced EMT in human immortalized urothelial cell (SV-HUC-1 cell line) by inhibiting the ERK5/AP-1 pathway. Therefore, curcumin may inhibit the occurrence of EMT by repressing the expression of EMT-related transcription factors mediated by AP-1.…”

Section: Effects Of Several Common Natural Products On Tumor Emtmentioning

confidence: 99%

Recent progress on the effects of microRNAs and natural products on tumor epithelial–mesenchymal transition

He¹,

Xiang²,

Zhang³

et al. 2017

OTT

Epithelial–mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection of EMT-associated marker molecules can also be used to judge the risk of metastasis and to evaluate patients’ prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene expression and protein translation through specific binding with the 3′ untranslated region of mRNA. In this review, we summarize the miRNAs that are reported to influence EMT through transcription factors such as ZEB, SNAIL, and TWIST, as well as some natural products that regulate EMT in tumors. Moreover, mutual inhibition occurs between some transcription factors and miRNAs, and these effects appear to occur in a complex regulatory network. Thus, understanding the role of miRNAs in EMT and tumor growth may lead to new treatments for malignancies. Natural products can also be combined with conventional chemotherapy to enhance curative effects.