2',3'-dimethoxyflavanone induces apoptosis accompanied by caspase-8 activation mediated by ubiquitination in breast cancer stem-like cells (BCSCs)
- Abstract
- The cytotoxicities of 13 flavonoids were tested in the breast cancer stem-like cell MCF-7-SC. Among them, 2',3'-dimethoxyflavanone (DMF) showed the highest toxicity. DMF triggered apoptosis by activating caspase-9, -3, -8, and cleaved PARP. In addition, DMF induces a dramatic increase in the conversion of LC3, a well-known marker for autophagy. However, co-treatment with chloroquine, the lysosomal inhibitor that blocks autophagic degradation did not show any change in the degree of LC3 conversion, implying that LC3 could play a role in the non-autophagic cell death of MCF-7-SC. In the present study, we found that DMF induces the ubiquitination of caspase-8 accompanied by the interaction between caspase-8 and LC3, which leads to the aggregation and self-activation of caspase-8. Consistent with this, co-treatment of DMF with 3MA, an inhibitor of LC3 lipidation reduced the activation of caspase-8. Our findings provide new insights into the anti-cancer activity of DMF in breast cancer stem cell through apoptosis in company with LC3 conversion.
- Author(s)
- TRAN ANH THAO
- Issued Date
- 2014
- Awarded Date
- 2014. 2
- Type
- Dissertation
- URI
- http://dcoll.jejunu.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000006635
- Alternative Author(s)
- 트란안타오
- Affiliation
- 제주대학교 대학원
- Department
- 대학원 응용생명공학과
- Advisor
- 김소미
- Table Of Contents
- 1. INTRODUCTION 1
2. MATERIALS AND METHODS 5
2.1 Reagents 5
2.2 Cell lines and Cell culture 5
2.3 Cytotoxicity 5
2.4 Cytometric analysis 6
2.5 Morphology 6
2.6 Western blot analysis 7
2.7 Immunoprecipitation 7
2.8 Colocalization assay 8
2.9 Statistics 8
3. RESULTS 9
3.1 Characteristics of the breast cancer stem cell MCF-7-SC 9
3.2. 2',3'-dimethoxyflavanone induced cell death through apoptotic pathway 15
3.3 2',3'-dimethoxyflavanone induced caspase-8 activation through ubiquitination system 19
3.4 Caspase-8 activation is regulated by LC3-ubiquitin-like protein 25
4. DISCUSSION 34
REFERENCES 38
- Degree
- Master
- Publisher
- 제주대학교 대학원
- Citation
- TRAN ANH THAO. (2014). 2',3'-dimethoxyflavanone induces apoptosis accompanied by caspase-8 activation mediated by ubiquitination in breast cancer stem-like cells (BCSCs)
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