Abstract | BACKGROUND: 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 Homo Sapiens Thrombospondin 1 (THBS-1) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-β1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 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 THBS-1 expression. Moreover, tetrac suppressed TGF-β expression combined with heteronemin to further enhance antiproliferation and anti- metastasis in oral cancer cells.
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Authors | 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 |
Journal | Marine drugs
(Mar Drugs)
Vol. 18
Issue 7
(Jul 02 2020)
ISSN: 1660-3397 [Electronic] Switzerland |
PMID | 32630719
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Terpenes
- heteronemin
- tetraiodothyroacetic acid
- Thyroxine
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Topics |
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Carcinoma
(drug therapy)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Gingival Neoplasms
(drug therapy)
- Humans
- Terpenes
(administration & dosage, pharmacology)
- Thyroxine
(administration & dosage, analogs & derivatives, pharmacology)
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