Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/97751
標題: α-蒎烯透過TNF-α/RIP訊息傳遞路徑誘導人類非小細胞肺癌程序性細胞壞死與抑制癌細胞轉移
α-Pinene induces TNF-α/RIP-dependent necroptosis and inhibits metastasis in human non-small-cell lung cancer
作者: 黃雅翎
Ya-Ling Huang
關鍵字: α-蒎烯;人類非小細胞肺癌;癌細胞轉移;α-Pinene;human non-small-cell lung cancer;EMT
引用: 1 et.al., X. N. Meta-Analysis and Systematic Review in Environmental Tobacco Smoke Risk of Female Lung Cancer by Research Type. Int J Environ Res Public Health. 15 (2018). 2 Chen HY, e. a. R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability. J Clin Oncol. 33, 2303-2310 (2015). 3 Nan-Yung Hsu, e. a. Human papillomavirus and non-small cell lung cancer. Thoracic Cancer 4, 345-353 (2013). 4 Ranjit S, e. a. Recent advances in cancer outcomes in HIV-positive smokers. F1000Res. (2018). 5 Denholm, R. et al. Is Previous Respiratory Disease a Risk Factor for Lung Cancer? American Journal of Respiratory and Critical Care Medicine 190, 549-559 (2014). 6 Chiu, C.-F. et al. NF-κB–driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance. Proceedings of the National Academy of Sciences 113, E2526-E2535 (2016). 7 Okimoto, R. A. et al. Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer. Proceedings of the National Academy of Sciences 113, 13456-13461 (2016). 8 Katiyar C, G. A., Kanjilal S, Katiyar S. Drug discovery from plant sources: an integrated approach. Ayu 33, 10-19 (2012). 9 Olaku O, W. J. Herbal therapy use by cancer patients: a literature review on case reports. Eur J Cancer 47, 508-514 (2011). 10 Zhao, Y., Chen, R., Wang, Y. & Yang, Y. α-Pinene Inhibits Human Prostate Cancer Growth in a Mouse Xenograft Model. Chemotherapy 63, 1-7 (2018). 11 Bahramsoltani, R., Farzaei, M. H., Oveissi, V. & Rahimi, R. in Cancer Genetics and Psychotherapy (ed Parvin Mehdipour) 951-980 (Springer International Publishing, 2017). 12 Khan MA, e. a. Pharmacological evidences for cytotoxic and antitumor properties of Boswellic acids from Boswellia serrata. J Ethnopharmacol. 191, 315-323 (2016). 13 Yang, H. et al. α-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABAA-benzodiazepine Receptors. Molecular Pharmacology 90, 530-539 (2016). 14 Kang, E. et al. α-Pinene inhibits tumor invasion through downregulation of nuclear factor (NF)-κB-regulated matrix metalloproteinase-9 gene expression in MDA-MB-231 human breast cancer cells. Applied Biological Chemistry 59, 511-516 (2016). 15 Jin, K.-S. et al. α-pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells. Food Science and Biotechnology 19, 1325-1332 (2010). 16 Z. Zhang, S. G., X. Liu, X. Gao. Synergistic Antitumor Effect of α-pinene and β-pinene with Paclitaxel against Non-small-cell Lung Carcinoma (NSCLC). Drug Res. 65, 214-218 (2015). 17 Silva, A. C. R. d. et al. Biological Activities of a-Pinene and β-Pinene Enantiomers. Molecules 17 (2012). 18 Elmore, S. Apoptosis: A Review of Programmed Cell Death. Toxicologic pathology 35, 495-516 (2007). 19 Syntichaki, P. & Tavernarakis, N. Death by necrosis: Uncontrollable catastrophe, or is there order behind the chaos? EMBO Reports 3, 604-609 (2002). 20 Linkermann, A. & Green, D. R. Necroptosis. The New England journal of medicine 370, 455-465 (2014). 21 Weinlich, R., Oberst, A., Beere, H. M. & Green, D. R. Necroptosis in development, inflammation and disease. Nature Reviews Molecular Cell Biology 18, 127 (2016). 22 Chen, D., Yu, J. & Zhang, L. Necroptosis: an alternative cell death program defending against cancer. Biochimica et biophysica acta 1865, 228-236 (2016). 23 Mao-Bin Meng, H.-H. W. e. a. Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy. Oncotarget 7, 57391-57413 (2016). 24 al., H. B. e. TNF and ROS Crosstalk in Inflammation. Trends in Cell Biology 26, 249-261 (2016). 25 Zhang, Y. et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nature Communications 8, 14329 (2017). 26 RA, C. C. W. A perspective on cancer cell metastasis. Science 331, 1559-1564 (2011). 27 Dominic Fan, S.-J. K., Robert L. Langley, and Isaiah J. Fidler. 2009. Drug Resistance in Cancer Cells (Metastasis and Drug Resistance). 28 Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation 119, 1420-1428 (2009). 29 Popper, H. H. Progression and metastasis of lung cancer. Cancer Metastasis Reviews 35, 75-91, doi:10.1007/s10555-016-9618-0 (2016). 30 Lo, U.-G., Lee, C.-F., Lee, M.-S. & Hsieh, J.-T. The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression. International Journal of Molecular Sciences 18, 2079 (2017). 31 NR, J. DNA damage by reactive species: Mechanisms, mutation and repair. J. Biosci. 37, 503-517 (2012). 32 Yang, I. T. L. C. C. L. Y. C. W. C. M. TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways. J Cell Physiol. 224, 454-464 (2010). 33 Videla, P. C. R. V. L. A. Nrf2‐regulated phase‐II detoxification enzymes and phase‐III transporters are induced by thyroid hormone in rat liver. Biofactors 39, 514-521 (2013). 34 Patial, N. P. a. S. Tumor Necrosis Factor-α Signaling in Macrophages. Crit Rev Eukaryot Gene Expr. 20, 87-103 (2010
摘要: 
肺癌是國人十大癌症死因之首,也是造成全世界最多人死亡的癌症,肺癌致死的主因為確診時惡性腫瘤通常已轉移,能存活超過五年的患者僅有16%。目前臨床使用的標靶藥物受到不同肺癌突變型態與抗藥性的影響而使效果受到限制,因此本研究的目的在於探討具有抑癌潛力的小分子精油的相關分子機制,以及是否能抑制高轉移性肺癌細胞的轉移,作為人類非小細胞肺癌新的治療藥物。單萜烯類α-Pinene是乳香精油的主要成分,過去研究已知其具有抗菌、抗發炎與抗癌等生物活性。根據本研究的結果證明,α-Pinene可以有效抑制A549人類非小細胞肺癌細胞株的存活率,並且以TNF-α/RIP訊息傳遞路徑誘導A549細胞走向程序細細胞壞死(Necroptosis),同時產生大量Reactive oxygen species (ROS),造成A549細胞內DNA受損。低濃度的α-Pinene可以有效抑制A549細胞爬行與侵襲的能力,並影響epithelial-mesenchymal transition (EMT)相關蛋白質的表現量來抑制A549細胞的轉移。

Lung cancer is the leading cause of cancer-related deaths in the world. The 5-y survival rate for lung cancer is around 16% of diagnosed cases. Much of the lethality of lung cancer is due to frequent diagnosis of the malignancy at the metastatic stage. α-Pinene is one of the members of monoterpene and is present in frankincense essential oil. a-Pinene have been attributed biological properties, including antimicrobial , antihypertensive, antinociceptive , and anti-inflammatory. Aims of this study are trying to examine the antitumor effect of α-Pinene in A549 human non-small-cell lung cancer (NSCLC) cell. In this study, we showed that α-Pinene inhibits A549 cell viability inducing necroptosis as evidenced by MTT assay ,flow cytometric analysis and western blot . We identify α-Pinene triggers A549 necroptosis through TNF-α/RIP-dependent signaling pathway,and induces reactive oxygen species (ROS) generation that causes A549 cells DNA damage,then we test whether α-Pinene affects metastasis of A549 cells. We found that low concentration of α-Pinene can significantly inhibit migration and invasion ability in A549 cells. These findings provide an in-depth insight into the molecular mechanism of α-Pinene in the treatment of human non-small-cell lung cancer.
URI: http://hdl.handle.net/11455/97751
Rights: 同意授權瀏覽/列印電子全文服務,2021-08-10起公開。
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