Abstract
Sinulariolide is a natural product extracted from the cultured-type soft coral Sinularia flexibilis, and possesses bioactivity against the movement of several types of cancer cells. However, the molecular pathway behind its effects on human bladder cancer remain poorly understood. Using a human bladder cancer cell line as an in vitro model, this study investigated the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was concentration-dependent. Furthermore, the protein expressions of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, as well as urokinase, were significantly decreased after 24-h sinulariolide treatment. Meanwhile, the increased expression of tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 were in parallel with an increased concentration of sinulariolide. Finally, the expressions of several key phosphorylated proteins in the mTOR signaling pathway were also downregulated by sinulariolide treatment. Our results demonstrated that sinulariolide has significant effects against TSGH-8301 cell migration/invasion, and its effects were associated with decreased levels of MMP-2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression. The inhibitory effects were mediated by reducing phosphorylation proteins of the PI3K, AKT, and mTOR signaling pathway. The findings suggested that sinulariolide is a good candidate for advanced investigation with the aim of developing a new drug for the treatment of human bladder cancer.
Highlights
Human bladder cancer is one of the most common cancers in the United States [1] and the ninth most common worldwide [2], accounting for approximately 5% of the mortality rate of all types of cancer in the US
Before studying how sinulariolide affects cell migration and invasion, we first examined the cytotoxicity of sinulariolide against human bladder cancer TSGH-8301 cells
As a 20% reduction of the cell viability effect was seen in cells treated with a concentration of 10 μM, concentrations of 5, 7.5, and 10 μM were used in subsequent experiments in this study to ensure that120 the inhibitory effects of sinulariolide on TSGH-8301 cell migration and invasionMar
Summary
Human bladder cancer is one of the most common cancers in the United States [1] and the ninth most common worldwide [2], accounting for approximately 5% of the mortality rate of all types of cancer in the US. The majority of human bladder cancers are diagnosed as urothelial carcinoma, known as transitional. The migration and invasion of metastatic carcinoma cells have been found to lead to destruction of the extracellular matrix (ECM), and several signal transduction pathways are known to be involved in the processes. Two proteolytic enzymes—matrix metalloproteinases (MMPs) MMP-2 and MMP-9—have been found to have extensively elevated levels in malignant tumors Expressions of these enzymes are major characteristics of malignant invasion and metastasis of cancer cells, as these enzymes are able to function to degrade the ECM, and may promote the penetration of cancer cells into the basement membrane. Inhibition of the protein expressions and enzyme activities of MMP-2/-9 and urokinase is considered to represent a potential therapeutic strategy to suppress cancer metastasis. Our results provided valuable information related to the use of sinulariolide in bladder cancer drug development
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
