Radiosensitization of clioquinol and zinc in human cervical cancer cell lines / 中华放射医学与防护杂志

Objective To investigate the radiosensitization effects of the combination treatment of clioquinol (CQ) and zinc on human cervical cell line HeLa in vitro.Methods Cells were divided into the 4 groups:controls,drug,radiation,and combined drug and radiation group.Cytotoxic effect of CQ and zinc on cell viability was determined by CCK-8 assay.Radiosensitization effect of CQ and zinc on HeLa cells was detected by colongenic assay,and the single-hit multi-target model was used to stimulate the doseresponse curve of survival and to calculate radiosensitization parameters.The cell cycle and apoptosis of HeLa cells were analyzed with flow cytometry.Luciferase reporter assay was used to study NF-κB activity of HeLa cells.Results The combination of CQ and zinc inhibited cell growth in a dose-dependent manner (F =188.00,P ＜ 0.01).The mean lethal dose was 3.16 and 2.04 Gy for radiation group and combined drug and radiation group,respectively,and hence the SER was 1.55.Compared with the radiation group,the ratio of G2-phase cells in the combined drug and radiation group decreased(t =10.39,P ＜ 0.05),the apoptosis rate increased at 24 h post-irradiation (t =5.64,P ＜ 0.01),and the NF-κB activity decreased (t =21.42,P ＜ 0.05).Compared to the control group,the NF-κB activity increased in the radiation group(t=6.23,P＜0.05),but decreased in the drug group(t =12.48,P＜0.05).Conclusions The combination of CQ and zinc could increase the radiosensitivity of HeLa cells by decreasing the ratio of G2-phase cells,increasing apoptosis and the inhibiting of NF-κB activity.

Effect of clioquinol on aggregation ofβ-amyloid in vitro / 国际药学研究杂志

Objective To study whether the metal chelator clioquinol (CQ) can affectβ-amyloid (Aβ) aggregation directly in vitro and whether this effect could be influenced by Zn2+. Methods In the study thioflavin T (Th-T) fluorescence was used to detect the aggregated Aβ. To eliminate the possible false positive results, the absorption spectrum (300 nm to 600 nm) of CQ was scanned, and a competitive binding assay was applied to determine whether Th-T and CQ had the same binding site on Aβ. Circular dichroism spectroscopy was used to detect β-sheet formation of Aβ. Results CQ could decrease the fluorescence intensity, when incubated with monomer Aβor aggregated Aβfor 24 h. Absorption spectra indicated that CQ had no specific absorption peak at 450 nm and 485 nm. Competitive binding assay showed that CQ and Th-T did not bind the same site on Aβ. CD spectra showed that CQ could decrease theβ-sheet formation of Aβ. When incubated with monomer Aβ, CQ decreased the fluorescence intensity in a dose dependent manner, and the IC50 were 6.1μmol/L (without Zn2+) and 4.3μmol/L (with Zn2+);When incubated with aggregated Aβ, CQ decreased the fluorescence intensity in a dose dependent mannerand, and the IC50 was 7.5μmol/L (without Zn2+) and 6.1μmol/L (with Zn2+). Conclusion CQ can inhibit the aggregation of monomer Aβand depolymerize the aggregated Aβdirectly in vitro. Zn2+has little influence on the effect of CQ on Aβ.

Effect of clioquinol on aggregation of β-amyloid in vitro / 国际药学研究杂志

Objective To study whether the metal chelator clioquinol (CQ) can affect β-amyloid (Aβ) aggregation directly in vitro and whether this effect could be influenced by Zn2c. Methods In the study thioflavin T (Th-T) fluorescence was used to detect the aggregated Aβ. To eliminate the possible false positive results, the absorption spectrum (300 nm to 600 nm) of CQ was scanned, and a competitive binding assay was applied to determine whether Th-T and CQ had the same binding site on Aβ. Circular dichroism spectroscopy was used to detect β-sheet formation of Aβ. Results CQ could decrease the fluorescence intensity, when incubated with monomer Aβ or aggregated Aβ for 24 h. Absorption spectra indicated that CQ had no specific absorption peak at 450 nm and 485 nm. Competitive binding assay showed that CQ and Th-T did not bind the same site on Aβ. CD spectra showed that CQ could decrease the β-sheet formation of Aβ. When incubated with monomer Aβ, CQ decreased the fluorescence intensity in a dose dependent manner, and the IC50 were 6.1 "mol/L (without Zn2c) and 4.3 "mol/L (with Zn2c); When incubated with aggregated Aβ, CQ decreased the fluorescence intensity in a dose dependent mannerand, and the IC50 was 7.5 "mol/L (without Zn2c) and 6.1 "mol/L (with Zn2c). Conclusion CQ can inhibit the aggregation of monomer Aβ and depolymerize the aggregated Aβ directly in vitro. Zn2c has little influence on the effect of CQ on Aβ.