Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway
A marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2018-12-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/16/12/489 |
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| author | Hung-Yun Lin Shu-Leei Tey Yih Ho Yung-Tang Chin Kuan Wang Jacqueline Whang-Peng Ya-Jung Shih Yi-Ru Chen Yung-Ning Yang Yu-Cheng Chen Yi-Chang Liu Heng-Yuan Tang Yu-Chen SH Yang |
| author_facet | Hung-Yun Lin Shu-Leei Tey Yih Ho Yung-Tang Chin Kuan Wang Jacqueline Whang-Peng Ya-Jung Shih Yi-Ru Chen Yung-Ning Yang Yu-Cheng Chen Yi-Chang Liu Heng-Yuan Tang Yu-Chen SH Yang |
| author_sort | Hung-Yun Lin |
| collection | DOAJ |
| description | A marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against cholangiocarcinoma HuccT1 and SSP-25 cells. In vitro, heteronemin altered the abilities of cell adhesion and cell migration in HuccT1 and SSP-25 cell lines. It repressed messenger ribonucleic acid (mRNA) expression levels of transforming growth factor (TGF)-β, mothers against decapentaplegic homolog (SMAD) and Myc, whose protein products play important roles in regulating cell growth, angiogenesis, and metastasis. In addition, heteronemin altered several signaling pathways. The results indicate that heteronemin was able to modulate cell adhesion, the expression of extracellular matrix (ECM) receptors, the TGF-β pathway, cell motility, the membrane integration, metastasis response, matrix metalloproteinase (MMP) remodeling, the regulation of metabolism, sprouting angiogenesis, transcription factors, and vasculogenesis in cholangiocarcinoma cell lines. The results also suggest that it activated multiple signal transduction pathways to induce an anti-proliferation effect and anti-metastasis in cholangiocarcinoma. In conclusion, heteronemin may be used as a potential medicine for anticancer therapy. |
| first_indexed | 2024-04-14T02:30:39Z |
| format | Article |
| id | doaj.art-194124cfcd354affbaaedb107f3503f0 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-14T02:30:39Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-194124cfcd354affbaaedb107f3503f02022-12-22T02:17:41ZengMDPI AGMarine Drugs1660-33972018-12-01161248910.3390/md16120489md16120489Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β PathwayHung-Yun Lin0Shu-Leei Tey1Yih Ho2Yung-Tang Chin3Kuan Wang4Jacqueline Whang-Peng5Ya-Jung Shih6Yi-Ru Chen7Yung-Ning Yang8Yu-Cheng Chen9Yi-Chang Liu10Heng-Yuan Tang11Yu-Chen SH Yang12Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanDepartment of Pediatrics, E-DA Hospital, Kaohsiung 824, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanTaipei Cancer Center, Taipei Medical University, Taipei 11031, TaiwanTaipei Cancer Center, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanTaipei Cancer Center, Taipei Medical University, Taipei 11031, TaiwanTaipei Cancer Center, Taipei Medical University, Taipei 11031, TaiwanDepartment of Pediatrics, E-DA Hospital, Kaohsiung 824, TaiwanThe Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, TaiwanDivision of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USAJoint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, TaiwanA marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against cholangiocarcinoma HuccT1 and SSP-25 cells. In vitro, heteronemin altered the abilities of cell adhesion and cell migration in HuccT1 and SSP-25 cell lines. It repressed messenger ribonucleic acid (mRNA) expression levels of transforming growth factor (TGF)-β, mothers against decapentaplegic homolog (SMAD) and Myc, whose protein products play important roles in regulating cell growth, angiogenesis, and metastasis. In addition, heteronemin altered several signaling pathways. The results indicate that heteronemin was able to modulate cell adhesion, the expression of extracellular matrix (ECM) receptors, the TGF-β pathway, cell motility, the membrane integration, metastasis response, matrix metalloproteinase (MMP) remodeling, the regulation of metabolism, sprouting angiogenesis, transcription factors, and vasculogenesis in cholangiocarcinoma cell lines. The results also suggest that it activated multiple signal transduction pathways to induce an anti-proliferation effect and anti-metastasis in cholangiocarcinoma. In conclusion, heteronemin may be used as a potential medicine for anticancer therapy.https://www.mdpi.com/1660-3397/16/12/489heteronemincholangiocarcinomaTGF-β pathway |
| spellingShingle | Hung-Yun Lin Shu-Leei Tey Yih Ho Yung-Tang Chin Kuan Wang Jacqueline Whang-Peng Ya-Jung Shih Yi-Ru Chen Yung-Ning Yang Yu-Cheng Chen Yi-Chang Liu Heng-Yuan Tang Yu-Chen SH Yang Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway Marine Drugs heteronemin cholangiocarcinoma TGF-β pathway |
| title | Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway |
| title_full | Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway |
| title_fullStr | Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway |
| title_full_unstemmed | Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway |
| title_short | Heteronemin Induces Anti-Proliferation in Cholangiocarcinoma Cells via Inhibiting TGF-β Pathway |
| title_sort | heteronemin induces anti proliferation in cholangiocarcinoma cells via inhibiting tgf β pathway |
| topic | heteronemin cholangiocarcinoma TGF-β pathway |
| url | https://www.mdpi.com/1660-3397/16/12/489 |
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