전립선암 세포주인 PC-3에서 cordycepin에 의해 유도된 세포 내 칼슘농도 변화와 미토콘드리아 기능 상실을 통한 세포사멸 유도

국문 초록 (Abstract)

Cordycepin은 동충하초로부터 분리한 생리활성 물질로써 항암활성을 가진다고 보고되어 있다. 하지만 그 정확한 항암 기전은 아직 확실하게 밝혀져 있지 않다. 이에 인간 전립선 암 세포주인 PC-3 세포를 이용하여 apoptosis와 그에 관련한 경로를 조사함으로써 cordycepin의 항암효과를 연구하였다. MTT assay를 통해 세포독성을 알아보았고 Annexin-V/PI 염색과 Ca²? 농도, ROS의 생성, MMP의 변화를 관찰하여 apoptosis 경로를 확인하였다. 뿐만 아니라 Western blot analysis를 이용하여 apoptosis와 관련된 단백질의 발현 정도를 확인하였다. 본 연구의 결과에서 cordycepin은 apoptosis 관련 단백질의 발현을 조절함으로써 apoptosis와 관련이 있음을 확인할 수 있었고, 미토콘드리아 관련 apoptosis 경로를 확인한 결과, ROS의 생성, Ca²?의 증가 그리고 미토콘드리아 막 전위의 붕괴를 통해 apoptosis 기전이 유도됨을 알 수 있었다. 이상의 결과로부터 cordycepin은 PC-3 세포에 대하여 ROS와 Ca²?의 농도 증가를 통해 MMP를 변화시켜 미토콘드리아 관련 apoptosis 기전을 거쳐 caspase의 활성을 증가시킴으로써 apoptosis를 유도함을 알 수 있었다.

다국어 초록 (Multilingual Abstract)

Cordycepin (3'-deoxyadenosine), a nucleoside derivative isolated from Cordyceps militaris, is reported to have antitumor effects. However, neither its molecular mechanism nor its molecular targets are well understood. In the present study, molecular mechanisms for the anti-tumor effects of cordycepin were investigated in human prostate cancer PC-3 cells. The MTT assay was used to detect cell viability. Annexin V/FITC assay, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and Ca²? flux were used to assess for the presence of apoptosis. Western blot analysis was used to detect protein expression. Treatment of cordycepin resulted in significantly decreased cell viability of PC-3 cells in a dose- and time-dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in significant mitochondrial dysfunction, ROS production, and elevation of Ca²? concentrations. These phenomena were followed activation of caspase-3, subsequently leading to PARP cleavage and cell apoptosis. Taken together, cordycepin induces apoptosis in PC-3 cells through regulation of a mitochondrial mediated pathway.

목차 (Table of Contents)

• 서론
• 재료 및 방법
• 결과 및 고찰
• 감사의 글
• References
• 초록

참고문헌 (Reference)

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