Objective： To investigate the As4S4 induced growth inhibition and apoptosis in HeLa cells and its possible relationship with cyclooxygenase-2 （COX-2）. Methods： HeLa cells were treated with various concentrations ...Objective： To investigate the As4S4 induced growth inhibition and apoptosis in HeLa cells and its possible relationship with cyclooxygenase-2 （COX-2）. Methods： HeLa cells were treated with various concentrations （7.5, 15, 30, 60 mg/L） of As4S4 at different times （12, 24, 36, 48, 60 h）. Cell growth was measured by MTT. Apoptosis was detected by double staining flow cytometry （FCM）. Levels of PGE2 were measured by radioimmunoassay. The expression of COX-2 protein was examined by Western blot analysis. Results： After treated with different concentrations of As4S4, the growth of HeLa cells was suppressed significantly in a dose-and time-dependent manner. The IC50 of 24 h was 30 mg/L （P〈0.01）. As4S4 induced apoptosis with apoptosis rates at 8.13%-62.36% by flow cytometry （FCM） in a dose-dependent manners. The release of PGE2 was reduced in HeLa cells with the values being （70.56±2.03）, （48.58±2.28）, （29.25±1.57） and （18.02±1.04） respectively, significantly different compared with control group （3.15±0.01） （P〈0.01）. As4S4 also inhibited the activity and expression of COX-2 in a dose dependent manner and down-regulated the expression of COX-2 protein greatly. Conclusion： As4S4 could inhibit the proliferation and increase apoptosis in human HeLa cells. These effects may depend on the inhibition of the expression of COX-2 and PGE2 by As4S4.展开更多
Mineral medicine,especially those containing heavy metals,is one of the characteristics of traditional Chinese medicine.A famous mineral medicine,realgar,containing heavy metal arsenic with a chemical formula of As4S4...Mineral medicine,especially those containing heavy metals,is one of the characteristics of traditional Chinese medicine.A famous mineral medicine,realgar,containing heavy metal arsenic with a chemical formula of As4S4,has the function of detoxification,killing bacteria and viruses,and eliminating dampness and phlegm.Different As4S4 isomers are likely to have different drug effects and pharmacological actions.Therefore,it is of great scientific significance to find more stable As4S4 isomers.In view of this,ab initio molecular orbital theory and density functional theory(DFT)have been used to study ten isomers of As4S4 at the B3LYP/6-31 G*,B3LYP/6-311+G*,B3LYP/6-311+G(3 df,2 p)and MP2/(6-311+G*,LanL2 MB)levels of theory.In addition to the two isomers having been studied previously,eight new isomers were investigated in the present paper.All the ten As4S4 isomers were proved to be true local minima on their potential energy surfaces.The calculated NICS values and molecular orbital analyses showed that,the D2d symmetric As4S4,isomer 1,may be s-aromatic.The study proves that ten As4S4 isomers are stable thermodynamically,and are highly desirable for the future theoretical study of realgar.展开更多
文摘Objective： To investigate the As4S4 induced growth inhibition and apoptosis in HeLa cells and its possible relationship with cyclooxygenase-2 （COX-2）. Methods： HeLa cells were treated with various concentrations （7.5, 15, 30, 60 mg/L） of As4S4 at different times （12, 24, 36, 48, 60 h）. Cell growth was measured by MTT. Apoptosis was detected by double staining flow cytometry （FCM）. Levels of PGE2 were measured by radioimmunoassay. The expression of COX-2 protein was examined by Western blot analysis. Results： After treated with different concentrations of As4S4, the growth of HeLa cells was suppressed significantly in a dose-and time-dependent manner. The IC50 of 24 h was 30 mg/L （P〈0.01）. As4S4 induced apoptosis with apoptosis rates at 8.13%-62.36% by flow cytometry （FCM） in a dose-dependent manners. The release of PGE2 was reduced in HeLa cells with the values being （70.56±2.03）, （48.58±2.28）, （29.25±1.57） and （18.02±1.04） respectively, significantly different compared with control group （3.15±0.01） （P〈0.01）. As4S4 also inhibited the activity and expression of COX-2 in a dose dependent manner and down-regulated the expression of COX-2 protein greatly. Conclusion： As4S4 could inhibit the proliferation and increase apoptosis in human HeLa cells. These effects may depend on the inhibition of the expression of COX-2 and PGE2 by As4S4.
基金supported by the National Natural Science Foundation of China(No.81403069)the Research and Development Fund of Beijing University of Chinese Medicine(No.2020072120050)。
文摘Mineral medicine,especially those containing heavy metals,is one of the characteristics of traditional Chinese medicine.A famous mineral medicine,realgar,containing heavy metal arsenic with a chemical formula of As4S4,has the function of detoxification,killing bacteria and viruses,and eliminating dampness and phlegm.Different As4S4 isomers are likely to have different drug effects and pharmacological actions.Therefore,it is of great scientific significance to find more stable As4S4 isomers.In view of this,ab initio molecular orbital theory and density functional theory(DFT)have been used to study ten isomers of As4S4 at the B3LYP/6-31 G*,B3LYP/6-311+G*,B3LYP/6-311+G(3 df,2 p)and MP2/(6-311+G*,LanL2 MB)levels of theory.In addition to the two isomers having been studied previously,eight new isomers were investigated in the present paper.All the ten As4S4 isomers were proved to be true local minima on their potential energy surfaces.The calculated NICS values and molecular orbital analyses showed that,the D2d symmetric As4S4,isomer 1,may be s-aromatic.The study proves that ten As4S4 isomers are stable thermodynamically,and are highly desirable for the future theoretical study of realgar.
