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Mar. Drugs 2017, 15(8), 238; doi:10.3390/md15080238

Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cells

1
Department of Nursing, Mei-ho University, Pingtung 91202, Taiwan
2
Graduate Institute of Applied Healthy and Biotechnology, Mei-ho University, Pingtung 91202, Taiwan
3
Taiwan Coral Research Center, National Museum of Marine Biology and Aquarium, Pingtung 94446, Taiwan
4
Department of Biological Technology, Mei-ho University, Pingtung 91202, Taiwan
The authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 17 April 2017 / Revised: 26 July 2017 / Accepted: 26 July 2017 / Published: 2 August 2017
(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)
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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. View Full-Text
Keywords: sinulariolide; human bladder cancer; migration; invasion; PI3K/AKT/mTOR signaling pathway sinulariolide; human bladder cancer; migration; invasion; PI3K/AKT/mTOR signaling pathway
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MDPI and ACS Style

Cheng, T.-C.; Din, Z.-H.; Su, J.-H.; Wu, Y.-J.; Liu, C.-I. Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cells. Mar. Drugs 2017, 15, 238.

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