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A Novel Synthetic Derivative of Deguelin, SH-174, Exhibits Anti-cancer Activities Against Non-small-cell Lung Cancer Cells : 새로운 deguelin 합성 유도체인 SH-174의 비소세포성 폐암세포에서의 항암 활성 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 김규원 | - |
dc.contributor.author | 김준용 | - |
dc.date.accessioned | 2019-03-13 | - |
dc.date.available | 2019-03-13 | - |
dc.date.issued | 2016-02 | - |
dc.identifier.other | 000000131841 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133385 | - |
dc.description | 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과, 2016. 2. 김규원. | - |
dc.description.abstract | The naturally occurring rotenoid, deguelin, has been studied to have a strong anti-cancer efficacy in various types of cancer for more than a decade. However, its intolerable toxicity at therapeutic dose and light-labile physical property deterred its development to be a clinical drug of use. Here, I report that SH-174, a novel synthetic derivative of deguelin, has a strong anti-cancer activity against several non-small-cell lung cancer (NSCLC) cells while having no or a less toxicity to human non-cancerous normal cells (e.g. BEAS-2B, ARPE-19, and HUVEC) than deguelin has. Several NSCLC cell lines were treated with or without SH-174 and subject to MTT assay, colony formation assay, and apoptosis assay | - |
dc.description.abstract | all of which treated with SH-174 exhibited significant inhibited results on the proliferation and survival of those cancer cells. Moreover, SH-174 reduced the ability of cancer cells to adapt to and survive under hypoxic cancer microenvironment by downregulating phosphorylation of Akt and MEK1/2, as well as HIF-1α protein level. To elucidate the target of oncogenic signaling in NSCLC cells by SH-174, I examined the AMPK-mTORC1 signaling axis which is harnessed by cancers for their rapid proliferation and survival. As a result, SH-174 induced the phosphorylation of AMPKα at Thr172, resulting in the inhibition of mTORC1 activity on cellular proliferation. This suggests SH-174 blocks the unchecked proliferation of cancer cells by modulating AMPK-mTORC1 signaling pathway. Thus, SH-174 is a new promising candidate for lung cancer therapy and further in vivo studies in animals are warranted. | - |
dc.description.tableofcontents | Chapter 1. Introduction 4
Chapter 2. Materials and Methods 9 Chapter 3. Results 14 Chapter 4. Discussion 32 Chapter 5. References 36 Abstract in Korean 45 | - |
dc.format | application/pdf | - |
dc.format.extent | 2465739 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 융합과학기술대학원 | - |
dc.subject | non-small-cell lung cancer | - |
dc.subject | NSCLC | - |
dc.subject | deguelin | - |
dc.subject | anti-cancer drug | - |
dc.subject | apoptosis | - |
dc.subject | hypoxia | - |
dc.subject | AMPK-mTORC1 | - |
dc.subject.ddc | 610 | - |
dc.title | A Novel Synthetic Derivative of Deguelin, SH-174, Exhibits Anti-cancer Activities Against Non-small-cell Lung Cancer Cells | - |
dc.title.alternative | 새로운 deguelin 합성 유도체인 SH-174의 비소세포성 폐암세포에서의 항암 활성 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Kim, Jun Yong | - |
dc.description.degree | Master | - |
dc.citation.pages | 46 | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2016-02 | - |
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