الفهرس | Only 14 pages are availabe for public view |
Abstract During the last few years in Egypt, all cancers increased in prevalence, incidence, and mortality but the increase in bladder was about 3 times as that for total cancer cases as illustrated in GLOBOCAN 2022 report. After diagnosis, a variety of treatment was available but some of these treatments could cause acquired resistance, thus highlighting the need to synthesize and develop a novel drug, that are capable of inhibiting bladder cancer. This study aimed to evaluate the cytotoxicity, cellular apoptosis and nuclease activities of [Cu (Me6tren) cl]PF6 on T-24 cells in addition to its possible radio-modification effect(s) in comparison to cisplatin. Copper amine complex was synthesized and characterized by IR & UV. The half inhibitory concentrations (IC50) of copper amine complex and cisplatin were 860.36 and 16.42 μM respectively using SRB assay after 48 hr. of treatment. Also, its radiomodification effect was assessed at 1, 2, 3, 4, 6 and 8 Gys. On the other hand, Twentieth, tenth, fifth concentrations of IC50 used to assess potential effect of copper amine complex on wound healing and cellular apoptosis assays. Results showed that the anti-tumor activity of Cisplatin is better than that of this study newly synthesized copper amine complex. After 48 hr., the irradiated cells recovered significantly, but the combination with cisplatin reduced the level of recovery. On the other hand, combination of IR and copper amine complex prevented any cell recovery. 20% of IC50 of cisplatin and Cu-amine complex increased significantly the percentage of late apoptosis phase to 4-5 times that of the control. We conclude that, the effect of copper transition metal complex on cell viability, cellular apoptosis, invasion, nuclease activity may be due to the complex structure not due to either the metal or the ligand individually. 6.2 Conclusion: According to this current study, we can conclude the followings: The anti-tumor activity of Cisplatin is better than that of this study newly synthesized copper amine complex. The combination between IR and this study newly synthesized copper amine complex (48 hr) improved the radiation cytotoxicity to about one half that of the radiation alone. After 48 hr, the irradiated cells recovered significantly, but the combination with cisplatin reduced the irradiated cell recovery. On the other hand, combination of IR and this study newly synthesized copper amine complex prevented any cell recovery. Cu-amine complex is able to bind to the DNA and affect its cleavage. 20% of IC50 of cisplatin and Cu-amine complex increased significantly the percentage of late apoptosis phase to 4-5 times that of the control. Invasion and migration by copper amine complex is time dependent and concentration independent. Summary, Conclusion and Recommendations 66 The effect of transition metal complexes on cell viability, cellular apoptosis, invasion, nuclease activity may be due to the complex structure not due to either the metal or the ligand individually. 6.3 Recommendations: Implementing the same experimental design using cells treated with the metal and the ligand as a control. Applying different concentrations of this study newly synthesized copper amine complex on the wound healing and cellular apoptosis assays. |