Biological Screening of Natural Compounds for Developing Anticancer Agents in Non-Small Cell Lung Cancer
비소세포성 폐암에서 항암제 개발을 위한 천연물 스크리닝

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자연과학대학 협동과정 유전공학전공
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서울대학교 대학원
Integrin α5β1MitochondriaNSCLCRecurrenceCancer metastasisCancer metabolism
학위논문 (석사)-- 서울대학교 대학원 : 자연과학대학 협동과정 유전공학전공, 2016. 2. 이호영.
After surgery or chemoradiation therapy, recurrence of non-small cell lung cancer is considered as a barrier to effective treatment. Several studies have reported that cancer metastasis and cancer metabolism augment NSCLC recurrence. Integrin α5β1 is overexpressed in metastatic NSCLC, and it leads to decrease survival rates. In terms of cancer metabolism, mitochondria play a role not only in ATP provision but also in aggressive behaviors of cancer cells. Therefore, novel compounds targeting cancer metastasis or cancer metabolism are in demand to prevent failure of primary treatment. In this study, we discovered compound A and compound B as targeting integrin α5β1 and mitochondria, respectively, through cell-based screens of a 160 natural compound library. Compound A suppresses cell adhesion on fibronectin which is an integrin α5β1 specific ligand, and shows acceptable values with integrin α5β1 on SwissDock docking. We identify that compound A reduces phosphorylation of FAK-Y397, an integrin dependent activation site, and its intracellular signaling molecules such as Src and AKT. Moreover, compound A disrupts the interaction between integrin α5β1 and Src. When it comes to cancer metabolism, compound B decreases intracellular ATP levels mediated by mitochondrial damage. Mitotracker, Mitosox, and TMRM data support that compound B negatively modulates mitochondrial function. Both compound A and compound B have anticancer activities confirmed by colony formation assays and propidium Iodide(PI) staining. In summary, our data suggest that compound A and compound B can be further developed to combat cancer metastasis and cancer metabolism as to cancer recurrence.
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College of Natural Sciences (자연과학대학)Program in Genetic Engineering (협동과정-유전공학전공)Theses (Master's Degree_협동과정-유전공학전공)
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