tailieunhanh - báo cáo khoa học: " 6-Nitro-2-(3-hydroxypropyl)-1H-benz[de] isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: 6-Nitro-2-(3-hydroxypropyl)-1H-benz[de] isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis | Mukherjee et al. Journal of Experimental Clinical Cancer Research 2010 29 175 http content 29 1 175 Journal of Experimental Clinical Cancer Research RESEARCH Open Access 6-Nitro-2- 3-hydroxypropyl -1H-benz de isoquinoline-1 3-dione a potent antitumor agent induces cell cycle arrest and apoptosis Asama Mukherjee1 Sushanta Dutta1 Muthiah Shanmugavel2 Dilip M Mondhe2 Parduman R Sharma2 Shashank K Singh2 Ajit K Saxena2 Utpal Sanyal1 Abstract Background Anticancer activities of several substituted naphthalimides 1H-benz de isoquinoline-1 3-diones are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series often N- hydroxyalkyl naphthalimides compounds 1a-j were evaluated as antitumor agents. Methods Compounds 1a-j were initially screened in MOLT-4 HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds 1d and 1i were further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound 1i treated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound 1i were measured at different time intervals. Morphology of the MOLT-4 cells after treatment with 1i was examined under light microscope and transmission electron microscope. 3H-Thymidine and 3H-uridine incorporation in S-180 cells in vitro following treatment with 8 pM concentration of compounds 1d and 1i were studied. Results 6-Nitro-2- 3-hydroxypropyl -1H-benz de isoquinoline-1 3-dione compound 1i has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC IC50 value 273 pM . Cell cycle analysis of .