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전세노사이드 F2에 의한 유방암 줄기세포에서의 Autophagy를 동반한 Apoptosis

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Alternative Title
Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells
Abstract
陣勢노사이드 Rb1의 미생물 반응산물인 진세노사이드 F2의 유방암 줄기세포에 대한 증식 억제 효능을 탐색하였다. 이 연구에서는 F2를 처리한 유방암 줄기세포에서 미토콘드리아 기능 장애와 함께 intrinsic apoptosis 경로를 통한 세포사멸 효과가 두드러지게 나타남을 확인하였다. 그리고 F2에 의한 AVO (acidic vesicular organelles)의 형성과 GFP-LCII형의 점증과 Atg7의 발현증가를 확인할 수 있었으며 이는 F2가 유방암 줄기세포에서 autophagy도 유발한다는 것을 제시하고 있다. Autophagy 억제제를 처리하였을 때 F2로 유도된 세포죽음은 더욱 향상되었지만, p53 억제제를 처리하였을 경우에는 autophagy와 apoptosis 현상의 감소로 인해 세포 죽음이 보호되었다. 따라서 이러한 연구 결과들은 유방암 줄기세포에 대한 F2의 항암 활성에 대해 새로운 견해를 제시하고 있으며, 따라서 F2의 약리학적인 연구와 합리적인 실용성에 기여할 것이다.
Ginsenoside F2, a microbial enzymatic product of ginsenoside Rb1, was assessed for its antiproliferative activity against breast cancer stem cells (CSCs). In this study, we revealed that F2 induced cell death with the mitochondrial dysfunction and the activation of caspase 9, PARP, Bax, Puma, p53. Concomitantly, F2 induced formation of acidic vesicular organelles (AVOs), recruitment of GFP-LC3-II to the autophagosomes, and elevation of Atg-7, suggesting that F2 initiated the autophagy in breast CSCs. Treatment of autophagy inhibitor enhanced the F2-induced cell death whereas blocking of p53 prevented both the autophagic and apoptotic activities, thus restored the cell viability. Together, our studies provided new insights regarding the anti-proliferative activity of F2 against breast cancer, and may contribute to rational utility and pharmacological study of F2 in future anti-cancer research.
Author(s)
메이타이트랭
Issued Date
2011
Awarded Date
2012. 2
Type
Dissertation
URI
http://dcoll.jejunu.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000005837
Alternative Author(s)
Mai, Thi Trang
Affiliation
제주대학교
Department
대학원 응용생명공학과
Advisor
김소미
Table Of Contents
ABSTRACT i
ABSTRACT IN KOREAN ii
CONTENTS iii
LIST OF TABLES iv
LIST OF FIGURES v
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
2.1. Reagents 4
2.2. Cell culture 5
2.3. Cell viability assay 6
2.4. Morphological study 6
2.5. Flow cytometric analysis 6
2.6. LC3-GFP transfection 7
2.7. Western blot analysis 7
2.8. Statistical analysis 8
III. RESULTS 9
3.1. Characteristics of breast CSCs following treatment with phytochemicals 9
3.2. Ginsenoside F2 induced apoptotic cell death in CSCs 13
3.3. Ginsenoside F2 induced autophagy in breast CSCs 19
3.4. CQ and PFT altered the apoptotic and autophagic signaling pathway in F2-treated CSCs 23
3.5. Ginsenoside F2 induced protective autophagy through modulation of p53 30
3.6. Suggested mechanism for F2-treated-breast CSCs 32
IV. DISCUSSION 34
REFERENCE 38
ACKNOWLEDGEMENT 49
Degree
Master
Publisher
제주대학교 대학원
Citation
메이타이트랭. (2011). 전세노사이드 F2에 의한 유방암 줄기세포에서의 Autophagy를 동반한 Apoptosis
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General Graduate School > Biomaterials Science and Technology
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