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

Abstract

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.

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR‑301a‑3p/STAT3 axis

“…These observations indicated that curcumin inhibited EMT by upregulating miR-301a-3p expression. It has been reported that curcumin suppressed EMT through the miR-200c/EPM5 axis and the ERK5/AP-1 and TET1-NKD-Wnt signaling pathways (60)(61)(62). Furthermore, our results indicated that the targeting of STAT3 by miR-301a-3p and the overexpression of STAT3 also reversed the inhibitory effects of curcumin on EMT in TPC-1 cells.…”

Curcumin reversed cigarette smoke extract-induced epithelial-to-mesenchymal transition of human bladder cancer cell UMUC3 through suppression of ERK1/2 pathway

“…Proofs have revealed that EMT participates in facilitating cancer aggression and migration [37]. The effects of CS on EMT and tumor developmental process have been discussed previously [7,8,[10][11][12][13][14][24][25][26][27][28][29][30]. As aforementioned, CSE elicited EMT in UMUC3 cells, as indicated by the morphologic alteration from epitheliums to mesenchyme cells.…”

“…Liang and colleagues found that curcumin reversed chronic tobacco smoke-triggered EMT in SV-HUC-1 cells and murine bladders [24,25]. Alike outcomes were found in mankind pulmonary carcinoma lineage cells ( H1299 and A549) [26], kidney cell cancer lineage cells (786-O and ACHN) [27], mouse lungs [28], mouse livers [29], and mouse stomach tissues [30]. It was reported that to evade chemoresistance, curcumin suppressed EMT and enhanced the antiproliferative capacity of conventional chemotherapeutics [23].…”

Regulation of the PTEN/PI3K/AKT pathway in RCC using the active compounds of natural products in vitro

“…Compared with synthetic drugs, treatment with natural products have fewer side effects, while exhibiting favorable outcomes ( 13 ). Although other studies have reported that several natural products, such as Epigallocatechin Gallate ( 19 ), quercetin ( 20 ), englerin A ( 21 ), honokiol ( 22 ), curcumin ( 23 ) and resveratrol ( 24 ) have shown beneficial results in preclinical studies of RCC, the research on the mechanism of the therapeutic activities of natural products on RCC is remains limited. The present study examined the antitumor effects of natural products on RCC.…”