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Open AccessArticle

Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma

Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan
Department of Food and Nutrition, Meiho University, Pingtung 91202, Taiwan
Yu Jun Biotechnology Co., Ltd., Kaohsiung 807, Taiwan
National Research Institute of Chinese Medicine, Taipei 112, Taiwan
National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan
Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2020, 18(6), 314;
Received: 17 May 2020 / Revised: 6 June 2020 / Accepted: 12 June 2020 / Published: 15 June 2020
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key strategy for successful intervention. A cembrane-type diterpene, flaccidoxide-13-acetate, isolated from marine soft coral Sinularia gibberosa, has been reported to have inhibitory effects against RT4 and T24 human bladder cancer invasion and cell migration. In this study, we investigated its suppression effects on tumor growth and metastasis of human HCC, conducting Boyden chamber and Transwell assays using HA22T and HepG2 human HCC cell lines to evaluate invasion and cell migration. We utilized gelatin zymography to determine the enzyme activities of matrix metalloproteinases MMP-2 and MMP-9. We also analyzed the expression levels of MMP-2 and MMP-9. Additionally, assays of tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), the focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway, and the epithelial-mesenchymal transition (EMT) process were performed. We observed that flaccidoxide-13-acetate could potentially inhibit HCC cell migration and invasion. We postulated that, by inhibiting the FAK/PI3K/Akt/mTOR signaling pathway, MMP-2 and MMP-9 expressions were suppressed, resulting in HCC cell metastasis. Flaccidoxide-13-acetate was found to inhibit EMT in HA22T and HepG2 HCC cells. Our study results suggested the potential of flaccidoxide-13-acetate as a chemotherapeutic candidate; however, its clinical application for the management of HCC in humans requires further research. View Full-Text
Keywords: flaccidoxide-13-acetate; hepatocellular carcinoma; invasion; migration; epithelial-mesenchymal transition flaccidoxide-13-acetate; hepatocellular carcinoma; invasion; migration; epithelial-mesenchymal transition
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Wu, Y.-J.; Wei, W.-C.; Dai, G.-F.; Su, J.-H.; Tseng, Y.-H.; Tsai, T.-C. Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma. Mar. Drugs 2020, 18, 314.

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