Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/97743
標題: 可能抑癌化合物的機制探討
Analyzing the biochemical mechanisms of anticancer compounds
作者: 林瑜芳
Yu-Fang Lin
關鍵字: 癌症;藥物;老藥新用;Cancer;drug;drug reposition
引用: 1. P. A. DiSilvestro, J. M. DiSilvestro, W. Lernhardt, M. Pfahl, R. S. Mannel, Treatment of cervical intraepithelial neoplasia levels 2 and 3 with adapalene, a retinoid-related molecule. J Low Genit Tract Dis 5, 33-37 (2001). 2. M. Ocker et al., Potentiated anticancer effects on hepatoma cells by the retinoid adapalene. Cancer Lett 208, 51-58 (2004). 3. X. N. Shi et al., Adapalene inhibits the activity of cyclin-dependent kinase 2 in colorectal carcinoma. Mol Med Rep 12, 6501-6508 (2015). 4. X. C. Xu, Tumor-suppressive activity of retinoic acid receptor-beta in cancer. Cancer Lett 253, 14-24 (2007). 5. X. Li et al., A novel stealth liposomal topotecan with amlodipine: apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia. J Control Release 112, 186-198 (2006). 6. Y. Zhang et al., Targeting therapy with mitosomal daunorubicin plus amlodipine has the potential to circumvent intrinsic resistant breast cancer. Mol Pharm 8, 162-175 (2011). 7. W.-p. LI, W.-j. HUANG, W.-j. SUN, Effect of Amlodipine on Cell Cycle of Murine Hepatocarcinoma H_ (22) Cells and Expression of Relevant Protein [J]. Chinese Journal of Biologicals 11, 025 (2010). 8. S. Suzuki et al., Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance. Anticancer Res 36, 5153-5161 (2016). 9. Y. Li et al., Multi-targeted therapy of cancer by niclosamide: A new application for an old drug. Cancer Lett 349, 8-14 (2014). 10. R. L. Stewart et al., S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide. Oncotarget 7, 34630-34642 (2016). 11. U. Sack et al., Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. J Natl Cancer Inst 103, 1018-1036 (2011). 12. D. Guillotin et al., Drug-Repositioning Screens Identify Triamterene as a Selective Drug for the Treatment of DNA Mismatch Repair Deficient Cells. Clin Cancer Res 23, 2880-2890 (2017). 13. L. Huang, S. Zhao, J. M. Frasor, Y. Dai, An integrated bioinformatics approach identifies elevated cyclin E2 expression and E2F activity as distinct features of tamoxifen resistant breast tumors. PLoS One 6, e22274 (2011). 14. V. N. Malashkevich et al., Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc Natl Acad Sci U S A 107, 8605-8610 (2010). 15. F. Fei, J. Qu, M. Zhang, Y. Li, S. Zhang, S100A4 in cancer progression and metastasis: A systematic review. Oncotarget 8, 73219-73239 (2017). 16. J. G. van den Boorn et al., Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy. J Invest Dermatol 131, 1240-1251 (2011). 17. J. G. van den Boorn et al., Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG. PLoS One 5, e10626 (2010). 18. J. A. Lieberman, Dopamine partial agonists: a new class of antipsychotic. CNS Drugs 18, 251-267 (2004). 19. X. Y. Wu et al., Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-kappaB Signaling Pathway. Cell Physiol Biochem 48, 2258-2272 (2018). 20. P. Jandaghi et al., Expression of DRD2 Is Increased in Human Pancreatic Ductal Adenocarcinoma and Inhibitors Slow Tumor Growth in Mice. Gastroenterology 151, 1218-1231 (2016). 21. X. Xiao, D. W. Melton, C. Gourley, Mismatch repair deficiency in ovarian cancer -- molecular characteristics and clinical implications. Gynecol Oncol 132, 506-512 (2014). 22. F. J. Couch et al., Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet 9, e1003212 (2013). 23. 癌症登記報告(103)。衛生福利部國民健康署。2018.07.取自 https://www.hpa.gov.tw/Pages/TopicList.aspx?nodeid=269 24. 癌症治療方式。林新醫院放射腫瘤科。2018.07.取自http://www.lshosp.com.tw:8000/dep1/articleDia.aspx?id=133 25. 健保引進標靶藥物,嘉惠癌症病患。行政院衛生署中央健康保險局電子報。2018.07.取自 https://www.nhi.gov.tw/epaper/ItemDetail.aspx?DataID=4528&IsWebData=0&ItemTypeID=3&PapersID=409&PicID 26. DrugBank。2018.07.取自 https://www.drugbank.ca/ 27. StatPearls - NCBI Bookshelf 。2018.07.取自https://www.ncbi.nlm.nih.gov/books/NBK430685/ 28. H. Rang, et al.(2006)。彩色圖說藥理學(劉人偉,譯)。台北:合記圖書出版社。(原著第五版出版於2003年) 29. 易大生物科技股份有限公司. Patent No. CN103961342A (31 January, 2013) 30. Lifeng Xu. Patent No. US 20130072553 A1 (11 June, 2009) 31. Stc.Unm. Patent No. WO2009148623 A2 (06 May, 2008) 32. STC.UNM. Patent No. US8835506 B2 (06 May, 2008) 33. 中國科學院上海藥物研究所. Patent No. CN104161759 A (16 May, 2013) 34. 中國科學院上海藥物研究所. Patent No. WO2014183673 A1 (16 May, 2013)
摘要: 
近年來有許多研究重新利用原有的非抗癌藥物來治療癌症,以節省藥物研發的各項成本,目前已有多項研究指出,部分人們長期使用的非抗癌用藥也具有治療癌症的效果,且售價比癌症用藥來的便宜許多,本實驗從1175個美國FDA核准藥物篩選出88、268、372、426、462、768、840、932、以及1162等9種具有抗癌效果的傳統非抗癌用藥,搜尋現有文獻以確認這些藥物在癌症治療方面的作用機制。結果發現:88可選擇性活化RAR或RXR,誘導癌細胞凋亡,也可作為CDK2抑制劑阻斷癌細胞生長。372與426可作為鈣離子通道阻斷劑,抑制p醣蛋白功能,並可阻斷細胞週期抑制癌細胞生長。462在癌症治療方面的作用機制目前仍不明確,有可能是與其作為多巴胺受體拮抗劑的功能相關。768對於不同癌細胞具有不同的作用途徑,包括:Wnt/β-catenin pathway、mTORC1 pathway、STAT3 pathway、NF-κB pathway以及Notch signal pathway。932會針對DNA修復功能異常的大腸結腸癌及子宮頸癌細胞產生毒性,治療效果主要與抗葉酸功能有關。1162的抗癌機制仍未確定,可能可誘導癌細胞自噬或抑制S100A4功能。268可誘導黑色素體自噬,並增強T細胞清除黑色素瘤功能。840的專利中只提到該藥物具有的抗癌功效,但並未提及作用機制。

In recent years, many studies have reused the original non-anticancer drugs to treat cancer, in order to save the cost of drug research and development. Today, many studies have pointed out that some people's long-term use of non-anticancer drugs also have the effect of treating cancer. And the price is much cheaper than that of cancer. This study get 9 drugs repurposing in cancer such as 88, 268, 372, 426, 462, 768, 840, 932, and 1162 from 1175 FDA-approved drugs. We search for existing literature to confirm the mechanism of action of these drugs in cancer treatment. It was found that 88 can selectively activate RAR or RXR to induce apoptosis in cancer cells, and can also act as a CDK2 inhibitor to block the growth of cancer cells. 372 and 426 act as calcium channel blockers, inhibit p-glycoprotein function, and block cell cycle and inhibit cancer cell growth. The mechanism of action of 462 in the treatment of cancer is still unclear and may be related to its function as a dopamine receptor antagonist. 768 has different pathways for different cancer cells, including: Wnt/β-catenin pathway, mTORC1 pathway, STAT3 pathway, NF-κB pathway, and Notch signal pathway. 932 is toxic to colorectal cancer and cervical cancer cells with abnormal DNA repair function, and the therapeutic effect is mainly related to anti-folate function. The anticancer mechanism of 1162 remains undetermined and may induce autophagy in cancer cells or inhibit S100A4 function. 268 induces autophagy of melanosomes and enhances T cell clearance of melanoma. The 840 patent only mentions the anticancer effect of the drug, but does not mention the mechanism of action.
URI: http://hdl.handle.net/11455/97743
Rights: 同意授權瀏覽/列印電子全文服務,2022-01-30起公開。
Appears in Collections:生命科學院碩士在職專班

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