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

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.