Anti-cancer effect of tectochrysin in NSCLC cells through overexpression of death receptor and inactivation of STAT3
| Autor: | Saet-Byul Oh, Bang Yeon Hwang, Young Wan Ham, Chul Ju Hwang, Suk-Young Song, Yu Yeon Jung, Hyung-Mun Yun, Jin Tae Hong, Ha Chang Sung, Sang-Bae Han, Jin-Mu Yi, Dong Hyun Park, Chang Hyun Sok |
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| Rok vydání: | 2014 |
| Předmět: |
STAT3 Transcription Factor
Cancer Research Small interfering RNA Lung Neoplasms Time Factors Receptor expression Apoptosis Biology Transfection Western blot Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans fas Receptor Phosphorylation STAT3 Receptors Tumor Necrosis Factor Member 25 Cell Proliferation Flavonoids Binding Sites Dose-Response Relationship Drug medicine.diagnostic_test Cell growth DNA Antineoplastic Agents Phytogenic Molecular biology Up-Regulation respiratory tract diseases Molecular Docking Simulation Oncology Mechanism of action Cancer cell Cancer research biology.protein RNA Interference medicine.symptom Signal Transduction |
| Zdroj: | Cancer Letters. 353:95-103 |
| ISSN: | 0304-3835 |
| Popis: | Phenolic compounds (flavonoids and phenolic acid derivatives) are the most important pharmacologically active ingredients, and these compounds could inhibit proliferation of human cancer cells by inducing of apoptotic cell death. Here we focused on the anticancer effects of tectochrysin on human non-small-cell lung cancer (NSCLC) cells and its mechanism of action. We analysed the activity of tectochrysin on NSCLC cells (A549 and NCI-H460) by use of Western blot analysis for major apoptotic proteins and death receptor expression. We also used EMSA for effects on STAT3 DNA binding activity. Tectochrysin (0-80 μM) suppressed the growth of A549 and NCI-H460 lung cancer cells by inducing of apoptotic cell death in a concentration dependent manner. Expression of DR3 and Fas as well as DR downstream pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax were concomitantly increased, but the expression of anti-apoptotic proteins; Bcl-2 was decreased in both cancer cells. In addition, tectochrysin treatment also inhibited phosphorylation of STAT3 in A549 and NCI-H460 cells. However, deletion of DR3 and Fas by small interfering RNA significantly reversed tectochrysin-induced cell growth inhibitory effect as well as down regulation of STAT3 in A549 and NCI-H460 lung cancer cells. Pull down assay and docking model showed interaction of tectochrysin with STAT3. We propose that tectochrysin leads to apoptotic cell death in NSCLC cells through activation of DR3 and Fas expression via inhibition of STAT3 phosphorylation. |
| Databáze: | OpenAIRE |
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