Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells
Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit <i>p53</i> expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, a...
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MDPI AG
2020-07-01
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| author | Chi-Hung Huang Tung-Yung Huang Wong-Jin Chang Yi-shin Pan Hung-Ru Chu Zi-Lin Li Sukanya Unson Yu-Tang Chin Chi-Yu Lin Haw-Ming Huang Chao-Nan Hsiung Fabio Gionfra Paolo De Vito Jens Z. Pedersen Sandra Incerpi Yi-Ru Chen Sheng-Yang Lee Hung-Yun Lin Paul J. Davis Jacqueline Whang-Peng Kuan Wang |
| author_facet | Chi-Hung Huang Tung-Yung Huang Wong-Jin Chang Yi-shin Pan Hung-Ru Chu Zi-Lin Li Sukanya Unson Yu-Tang Chin Chi-Yu Lin Haw-Ming Huang Chao-Nan Hsiung Fabio Gionfra Paolo De Vito Jens Z. Pedersen Sandra Incerpi Yi-Ru Chen Sheng-Yang Lee Hung-Yun Lin Paul J. Davis Jacqueline Whang-Peng Kuan Wang |
| author_sort | Chi-Hung Huang |
| collection | DOAJ |
| description | Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit <i>p53</i> expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates <i>p53</i> and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3’,5,5’-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. Results: Heteronemin inhibited not only expression of proliferative genes and <i>Homo Sapiens Thrombospondin 1</i> (<i>THBS-1</i>) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased <i>TGF-β1</i> expression in SCC-25 cells. Tetrac suppressed expression of <i>THBS-1</i> but not <i>p53</i> expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited <i>THBS-1</i> expression. Moreover, tetrac suppressed <i>TGF-β</i> expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells. |
| first_indexed | 2024-03-10T18:43:16Z |
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| language | English |
| last_indexed | 2024-03-10T18:43:16Z |
| publishDate | 2020-07-01 |
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| series | Marine Drugs |
| spelling | doaj.art-1befe3fe4a59400ca553949835de62512023-11-20T05:39:30ZengMDPI AGMarine Drugs1660-33972020-07-0118734810.3390/md18070348Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer CellsChi-Hung Huang0Tung-Yung Huang1Wong-Jin Chang2Yi-shin Pan3Hung-Ru Chu4Zi-Lin Li5Sukanya Unson6Yu-Tang Chin7Chi-Yu Lin8Haw-Ming Huang9Chao-Nan Hsiung10Fabio Gionfra11Paolo De Vito12Jens Z. Pedersen13Sandra Incerpi14Yi-Ru Chen15Sheng-Yang Lee16Hung-Yun Lin17Paul J. Davis18Jacqueline Whang-Peng19Kuan Wang20School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanCollege of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanDepartment of Sciences, University Roma Tre, 00146 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Sciences, University Roma Tre, 00146 Rome, ItalyGraduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USAGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, TaiwanBackground: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit <i>p53</i> expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates <i>p53</i> and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3’,5,5’-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. Results: Heteronemin inhibited not only expression of proliferative genes and <i>Homo Sapiens Thrombospondin 1</i> (<i>THBS-1</i>) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased <i>TGF-β1</i> expression in SCC-25 cells. Tetrac suppressed expression of <i>THBS-1</i> but not <i>p53</i> expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited <i>THBS-1</i> expression. Moreover, tetrac suppressed <i>TGF-β</i> expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.https://www.mdpi.com/1660-3397/18/7/348tetracheteroneminoral cancerantiproliferation |
| spellingShingle | Chi-Hung Huang Tung-Yung Huang Wong-Jin Chang Yi-shin Pan Hung-Ru Chu Zi-Lin Li Sukanya Unson Yu-Tang Chin Chi-Yu Lin Haw-Ming Huang Chao-Nan Hsiung Fabio Gionfra Paolo De Vito Jens Z. Pedersen Sandra Incerpi Yi-Ru Chen Sheng-Yang Lee Hung-Yun Lin Paul J. Davis Jacqueline Whang-Peng Kuan Wang Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells Marine Drugs tetrac heteronemin oral cancer antiproliferation |
| title | Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells |
| title_full | Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells |
| title_fullStr | Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells |
| title_full_unstemmed | Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells |
| title_short | Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells |
| title_sort | combined treatment of heteronemin and tetrac induces antiproliferation in oral cancer cells |
| topic | tetrac heteronemin oral cancer antiproliferation |
| url | https://www.mdpi.com/1660-3397/18/7/348 |
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