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악성 유방암 세포에서 CDDO-ME 처리 시 Ca2+ 유입에 매개된 소포체 팽창과 c-FLIP 감소를 통한 세포자살 유도
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 최경숙 | - |
| dc.contributor.author | 정수아 | - |
| dc.date.accessioned | 2019-10-21T07:30:15Z | - |
| dc.date.available | 2019-10-21T07:30:15Z | - |
| dc.date.issued | 2015-02 | - |
| dc.identifier.other | 19228 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/19040 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2015. 2 | - |
| dc.description.tableofcontents | I.INTRODUCTION 1 II.MATERIALS AND METHODS 6 A.Chemicals and antibodies 6 B.Cell culture of various cancer cell lines 7 C.Measurement of cell viability 7 D.Western blotting 7 E.Immunocytochemistry 8 F.Establishment of the stable cell lines in the fluorescence specifically mitochondria or endoplasmic reticulum 9 G.Measurement of ROS and mitochondrial superoxide anion 9 H.Measurement of cytosolic and mitochondrial Ca² levels 9 I.shRNA-mediated knockdown of proteins 10 J.Transmission electron microscopy 10 K.Reverse transcriptionPCR analysis 11 L.Statistical analysis 12 III. RESULTS 13 1.CDDO-ME demonstrates a potent anti-cancer effect on breast cancer cells 13 2.CDDO-ME induces paraptosis-like cellular vacuolation prior to morphologies features of apoptosis in breast cancer cells 17 3.Ca2+ influx is crucial for CDDO-ME-induced vacuolation and subsequent apoptotic cell death 40 4.Cross-modulation between Ca2+ influx and ROS generation critically contributes to CDDO-ME-induced vacuolation and subsequent apoptosis 51 5.c-FLIPL downregulation plays a critical role in CDDO-ME-induced apoptotic cell death, but not in vacuolation 58 6.Higher increase in intracellular Ca2+ and ROS levels as well as c-FLIP downregulation may contribute to a more potent anti-cancer effect of CDDO-ME, compared to CDDO 69 IV.DISCUSSION 73 V.REFERENCES 79 -국문요약- 90 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 악성 유방암 세포에서 CDDO-ME 처리 시 Ca2+ 유입에 매개된 소포체 팽창과 c-FLIP 감소를 통한 세포자살 유도 | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2015. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 770787 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000019228 | - |
| dc.subject.keyword | 세포자살 | - |
| dc.subject.keyword | CDDO-ME | - |
| dc.subject.keyword | 소포체 | - |
| dc.subject.keyword | 칼슘 | - |
| dc.subject.keyword | c-FLIP | - |
| dc.description.alternativeAbstract | Oleanolic acid-derived synthetic triterpenoids are a promising new class of compounds with antitumorigenic activity against various types of cancer cells. In this study, we show that methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-ME) triggered paraptosis-like cellular vacuolation, which was mainly derived from the dilation of the endoplasmic reticulum, but finally killed breast cancer cells via apoptosis. We found that the increase in intracellular Ca2+ levels preceded CDDO-ME-induced vacuolation and cell death. In addition, this increase was accompanied by the increase in reactive oxygen species (ROS) levels. Pretreatment with Ca2+ chelator, BAPTA, BAPTA-AM or antioxidant, N-acetylcysteine effectively blocked CDDO-ME-induced vacuolation and cell death, suggesting that Ca2+ influx and ROS generation are initial critical signals for CDDO-ME-induced anti-cancer effect. Moreover, CDDO-ME markedly reduced the protein levels of c-FLIPL. Overexpression of c-FLIPL did not affect CDDO-ME-induced vacuolation, but significantly attenuated CDDO-ME-induced cell death. Interestingly, CDDO-ME increased intracellular Ca2+ and ROS levels at much lower doses, compared to CDDO and CDDO rather increased the protein levels of c-FLIPL via its proteasome inhibitory activity. Taken together, our results clearly show that both intracellular Ca2+ influx, ROS generation and c-FLIP downregulation critically contribute to the potent anti-cancer effect of CDDO-ME in breast cancer cells. | - |
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