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Molecules 2018, 23(1), 58; https://doi.org/10.3390/molecules23010058

Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway

1
Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan
2
Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan
3
Department of Biological Technology, Meiho University, Pingtung 91202, Taiwan
4
National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan
5
Department of Nursing, Meiho University, Pingtung 91202, Taiwan
6
Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 16 November 2017 / Revised: 21 December 2017 / Accepted: 24 December 2017 / Published: 27 December 2017
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Abstract

Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, urokinase-type plasminogen activator receptor (uPAR), focal adhesion kinase (FAK), phosphatidylinositide-3 kinases (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, Ras homolog gene family, member A (Rho A), Ras, mitogen-activated protein kinase kinase 7 (MKK7) and mitogen-activated protein kinase kinase kinase 3 (MEKK3), and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in RT4 and T24 cells. This study revealed that flaccidoxide-13-acetate suppressed cell migration and invasion by reducing the expressions of MMP-2 and MMP-9, regulated by the FAK/PI3K/AKT/mTOR pathway. In conclusion, our study was the first to demonstrate that flaccidoxide-13-acetate could be a potent medical agent for use in controlling the migration and invasion of bladder cancer. View Full-Text
Keywords: flaccidoxide-13-acetate; bladder cancer cells; migration; invasion; matrix metalloproteinase flaccidoxide-13-acetate; bladder cancer cells; migration; invasion; matrix metalloproteinase
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Neoh, C.-A.; Wu, W.-T.; Dai, G.-F.; Su, J.-H.; Liu, C.-I.; Su, T.-R.; Wu, Y.-J. Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway. Molecules 2018, 23, 58.

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