Novel morpholin-3-one derivatives induced apoptosis and elevated the level of P53 and Fas in A549 lung cancer cells.
Previously, we found that nine kinds of new morpholin-3-one derivatives could inhibit the growth of A549 lung cancer cells in a dose-dependent manner, but how they performed their function remained unknown. In this paper, we studied the effects of the three more effective morpholin-3-one derivatives {4-(4-chlorophenyl)-6-((4-nitrophenoxy) methyl) morpholin-3-one (1); 6-(4-chlorophenoxy)-4-(4-methoxyphenyl) morpholin-3-one (2); and 6-((4-nitrophenoxy) methyl)-4-phenylmorpholin-3-one (3)} on the cell cycle distribution, apoptosis, and the level of P53 and Fas that are two kinds of important proteins in the regulation of A549 cell growth and apoptosis. According to the results of cell viability, we selected 40 microg/ml of morpholin-3-one derivatives as the most appropriate concentration for the following study. The results showed that the morpholin-3-one derivatives partly blocked the cells at G1 phase, induced apoptosis, and elevated the level of P53 and Fas proteins significantly. The effect of the morpholin-3-one derivates was associated with translocation of P53 and clustering of Fas. Our data suggested that the morpholin-3-one derivates might be promising tools for elucidating the molecular mechanism of lung cancer cell apoptosis and they will be very potential candidates for developing anti-cancer drugs.
He
Qiuxia
Q
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Zhu
Xingshang
X
Shi
Mei
M
Zhao
Baoxiang
B
Zhao
Jing
J
Zhang
Shangli
S
Miao
Junying
J
D017209:Apoptosis; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000378:metabolism*; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor / Q000032:analysis / Q000378:metabolism*
C521396:(4-(4-chlorophenyl)-6-((4-nitrophenoxy) methyl) morpholin-3-one); C521398:6-((4-nitrophenoxy) methyl)-4-phenylmorpholin-3-one; C521397:6-(4-chlorophenoxy)-4-(4-methoxyphenyl) morpholin-3-one; D009025:Morpholines; D009574:Nitro Compounds; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor