tailieunhanh - Báo cáo y học: "Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanom"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. | Hamsa and Kuttan Chinese Medicine 2011 6 11 http content 6 1 11 CHINESE MEDICINE RESEARCH Open Access Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma Thayele Purayil Hamsa and Girija Kuttan Abstract Background Harmine is a beta-carboline alkaloid from the plant Peganum harmala. Previous studies found that harmine inhibited metastasis of B16F-10 melanoma cells. This study aims to elucidate the role of harmine in apoptosis of B16F-10 cells. Methods B16F-10 melanoma cells were treated in the presence and absence of harmine in vitro. Morphological changes cell cycle and expression of various pro and anti- apoptotic genes were analyzed for the study of apoptosis. Results Morphological observation and DNA laddering assay showed that harmine treated cells displayed marked apoptotic characteristics such as nuclear fragmentation appearance of apoptotic bodies and DNA laddering fragment. TUNEL assay and flow cytometric analysis also confirmed apoptosis. Furthermore RT-PCR analysis showed that harmine induced apoptosis in B16F-10 melanoma cells by up-regulating Bax and activating Caspase-3 9 and p53 and down-regulating Bcl-2. Harmine also up-regulated Caspase-8 and Bid indicating that harmine affected both extrinsic and intrinsic pathways of apoptosis. This study also showed inhibitory effects of harmine on some transcription factors and pro- inflammatory cytokines that protect cell from apoptosis. Conclusion Harmine activates both intrinsic and extrinsic pathways of apoptosis and regulates some transcription factors and pro-inflammatory cytokines. Background Apoptosis programmed cell death occurs during normal development and tissue homeostasis or as a response to cellular insults and oncogenesis 1 . Apoptosis involves a sequence of specific morphological changes in a dying cell condensation of the cytoplasm and nuclear chromatin followed by breakage of cells into membrane bound apoptotic bodies containing a variety of .