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.

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.

• Authors: Choo-Aun Neoh, Wen-Tung Wu, Guo-Fong Dai, Jui-Hsin Su, Chih-I Liu, Tzu-Rong Su, Yu-Jen Wu
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 23 Issue 1 (Dec 27 2017) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 29280977 (Publication Type: Journal Article)

Chemical References

• Diterpenes
• Plant Extracts
• Tissue Inhibitor of Metalloproteinase-1
• flaccidoxide-13-acetate
• Tissue Inhibitor of Metalloproteinase-2
• Focal Adhesion Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Anthozoa (chemistry)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Diterpenes (chemistry, pharmacology)
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Humans
• Neoplasm Invasiveness (prevention & control)
• Phosphatidylinositol 3-Kinases (metabolism)
• Plant Extracts (chemistry, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (metabolism)
• Urinary Bladder Neoplasms (drug therapy)