FaDu 사람 두경부세포암에서 adenosine에 의한 항암효과

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with 600,000 cases diagnosed per year. HNSCC is responsible for high death rates worldwide every year. Adenosine, a purine nucleoside present in plasma and other extra-cellular organism acts as a regulatory molecule, by binding to G-protein associated cell-surface receptors, A1, A2 and A3. It is a regulatory factor with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. It has been shown to inhibition of cell proliferation and induction of apoptosis in the several cancer cells via intrinsic and extrinsic caspases dependent pathway. The purpose of this study was to understand the underlying mechanism adenosine-induced apoptosis in the FaDu human HNSCC. MTT viability was used to confirm the cell proliferation. Genomic DNA fragmentation and Hoechest staining were used to study the apoptotic morphology change of cells by adenosine treatment. Apoptosis analysis, annexin V and propidium iodide staining, Bax, Bcl-2, cleaved caspase-3 and PARP protein expressions were assessed to detect apoptosis. Adenosine significantly reduced cell proliferation in a dose-dependent manner in FaDu human HNSCC. However, normal oral fibroblast cell is not changed cell proliferation. It is investigated that down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. It is also confirmed to apoptotic property by morphological changes in the genomic DNA fragmentation and nuclei condensation. Moreover, adenosine induced apoptosis in FaDu human HNSCC which was determined by Annexin V- FlTC/PI staining. These results suggested that adenosine induce apoptosis in FaDu human HNSCC via the mitochondrial pathway. These data might suggest that adenosine could be used as a chemotherapy agent and adiuvent for human HNSCC