Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma
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...
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MDPI AG
2020-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/6/314 |
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| author | Yu-Jen Wu Wen-Chi Wei Guo-Fong Dai Jui-Hsin Su Yu-Hwei Tseng Tsung-Chang Tsai |
| author_facet | Yu-Jen Wu Wen-Chi Wei Guo-Fong Dai Jui-Hsin Su Yu-Hwei Tseng Tsung-Chang Tsai |
| author_sort | Yu-Jen Wu |
| collection | DOAJ |
| description | 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 <i>Sinularia gibberosa</i>, 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. |
| first_indexed | 2024-03-10T19:10:31Z |
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| language | English |
| last_indexed | 2024-03-10T19:10:31Z |
| publishDate | 2020-06-01 |
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| series | Marine Drugs |
| spelling | doaj.art-cc74296335804dfab17401d91a0473ac2023-11-20T03:51:32ZengMDPI AGMarine Drugs1660-33972020-06-0118631410.3390/md18060314Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular CarcinomaYu-Jen Wu0Wen-Chi Wei1Guo-Fong Dai2Jui-Hsin Su3Yu-Hwei Tseng4Tsung-Chang Tsai5Department of Beauty Science, Meiho University, Pingtung 91202, TaiwanNational Research Institute of Chinese Medicine, Taipei 112, TaiwanYu Jun Biotechnology Co., Ltd., Kaohsiung 807, TaiwanNational Museum of Marine Biology and Aquarium, Pingtung 94450, TaiwanNational Research Institute of Chinese Medicine, Taipei 112, TaiwanAntai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, TaiwanHepatocellular 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 <i>Sinularia gibberosa</i>, 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.https://www.mdpi.com/1660-3397/18/6/314flaccidoxide-13-acetatehepatocellular carcinomainvasionmigrationepithelial-mesenchymal transition |
| spellingShingle | Yu-Jen Wu Wen-Chi Wei Guo-Fong Dai Jui-Hsin Su Yu-Hwei Tseng Tsung-Chang Tsai Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma Marine Drugs flaccidoxide-13-acetate hepatocellular carcinoma invasion migration epithelial-mesenchymal transition |
| title | Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma |
| title_full | Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma |
| title_fullStr | Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma |
| title_full_unstemmed | Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma |
| title_short | Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma |
| title_sort | exploring the mechanism of flaccidoxide 13 acetate in suppressing cell metastasis of hepatocellular carcinoma |
| topic | flaccidoxide-13-acetate hepatocellular carcinoma invasion migration epithelial-mesenchymal transition |
| url | https://www.mdpi.com/1660-3397/18/6/314 |
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