Zeylenone represses the progress of human prostate cancer by downregulating the Wnt/β‑catenin pathway

Abstract

Prostate cancer (PCa) is one of the most common types of cancer in the urinary system in men. Zeylenone (Zey), a naturally occurring cyclohexene oxide, has an anticancer effect. In the present study, the role and potential mechanism of Zey in PCa were examined. The proliferative, invasive and migratory capacities of DU145 cells were analyzed using Cell Counting Kit-8, transwell and wound healing assays, respectively. The expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were determined with an ELISA. Reverse transcription-quantitative polymerase chain reaction and western blotting assays were performed to evaluate the expression levels of extracellular matrix, epithelial-mesenchymal transition and Wnt/β-catenin pathway-associated factors. In the present study, it was observed that Zey not only suppressed the viability of DU145 cells; however, it additionally attenuated the invasive and migratory capacities of cells in a concentration-dependent manner. Treatment of Zey decreased the expression levels of MMP-2, MMP-9 and fibronectin-1; whereas, it increased tissue inhibitor of metalloproteinases-1 and collagen-1 expression levels. Additionally, the vimentin expression level was downregulated, however, the epithelial-cadherin expression level was upregulated in cells treated with Zey. Furthermore, Zey decreased the expression levels of wnt5a, β-catenin and cyclin D1. In conclusion, the present results demonstrated that Zey decreased the viability and metastasis of human PCa cells (DU145), via the Wnt/β-catenin signaling pathway. Therefore, Zey may be applied as a novel drug for treating PCa in the future.

Natural Products as Anticancer Agents: Current Status and Future Perspectives

“…Similarly, punicalagin, a polyphenol, exhibited apoptotic activity and inhibited the proliferation of PC3 and LNCaP cells via upregulating caspase-3/-8 expressions and decreasing vascular network formation in the CAM model, which also confirmed its antiangiogenic effect [ 166 ]. Furthermore, Zeylenone isolated from Uvaria grandiflora Roxb decreased the cell viability, invasion, and metastatic growth of human PCa (DU145) cells by downregulating the Wnt/β-catenin pathway [ 167 ]. Moreover, mangiferin has been reported to possess immunomodulatory, apoptotic, antiangiogenic, and gene regulatory effects in vitro, ex vivo, and in vivo in different cancers, especially prostate cancer [ 168 ].…”

Matrix Metalloproteinases (MMPs) and Diabetic Foot: Pathophysiological Findings and Recent Developments in Their Inhibitors of Natural as well as Synthetic Origin

“…In the present study, Zey is reported to have anti-cancer activity against prostate cancer. Zeylenone has been reported to suppress the expression of MMP-2, MMP-9 and upregulate the expression of TIMP-1 and collagen-1 in DU145 cells [173]. Curcumin is a natural compound extracted from plant Curcuma longa (Zingiberaceae).…”

Development of S4A–BSA–Au NPs for enhanced anti-tumor therapy of canine breast cancer

“…Zeylenone (Zey) is a natural cyclohexene oxide compound isolated from Uvaria grandiflora Roxb 6 . Since the discovery of Zey in 1997, researchers have carried out multiple studies on its manufacturing processes (synthesis/semi-synthesis), pharmacodynamics and molecular mechanism, etc, and it was considered to be an anti-tumor candidate drug with great potential [7][8][9][10] . Studies have shown that Zey could induce a large number of cell apoptosis through mitochondrial apoptosis pathway and inhibit the invasion and migration of gastric cancer cells 11 .…”

“…6 Since the discovery of Zey in 1997, researchers have carried out multiple studies on its manufacturing processes (synthesis/semi-synthesis), pharmacodynamics, molecular mechanism, etc., and it was considered to be an anti-tumor drug candidate with great potential. [7][8][9][10] Studies have shown that Zey could induce signicant cell apoptosis through a mitochondrial apoptosis pathway and inhibit the invasion and migration of gastric cancer cells. 11 Furthermore, it was reported that Zey had signicant inhibitory activity against a variety of tumor cells, which was timedependent and dose-dependent, and its anti-tumor activity was similar to that of paclitaxel.…”