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https://scholarbank.nus.edu.sg/handle/10635/48641
DC Field | Value | |
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dc.title | INHIBITION OF DNA REPAIR FACTORS SENSITIZES HUMAN CANCER CELLS TO SILVER NANOPARTICLES TOXICITY: MECHANISTIC INSIGHTS AND IMPLICATIONS IN CANCER THERAPY | |
dc.contributor.author | LIM HUI KHENG | |
dc.date.accessioned | 2013-12-31T18:20:25Z | |
dc.date.available | 2013-12-31T18:20:25Z | |
dc.date.issued | 2013-08-02 | |
dc.identifier.citation | LIM HUI KHENG (2013-08-02). INHIBITION OF DNA REPAIR FACTORS SENSITIZES HUMAN CANCER CELLS TO SILVER NANOPARTICLES TOXICITY: MECHANISTIC INSIGHTS AND IMPLICATIONS IN CANCER THERAPY. ScholarBank@NUS Repository. | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/48641 | |
dc.description.abstract | Silver nanoparticles (Ag-np) are distinctively reported as toxic agent. This potentially detrimental toxicity of Ag-np can however be used to our advantage to enhance therapeutic efficacy of existing cancer drugs. We found that Ag-np induced more prominent dose-dependent decrease in cell viability in DNA-PKcs deficient or inhibited cells. The deficiency or inhibition of DNA-PKcs renders the cells with higher susceptibility to DNA damage and genome instability which in turn contributed to greater cell cycle arrest/cell death. These findings support the fact that DNA-PKcs is involved in the repair of Ag-np induced DNA damage. At mechanistic level, we found following DNA-PKcs inhibition, JNK pathway was insufficiently activated, abolishing the signalling events required for DNA repair. Localization of activated DNA-PKcs to damaged telomeres indicates the importance of DNA repair machinery at damaged telomeres. DNA-PKcs inhibition substantiates the damaging effect of Ag-np at telomeres in human cancer cells. These two phenomena are responsible for the greater sensitivity of the cancer cells towards Ag-np cytotoxicity. These results suggest inhibition of DNA-PKcs together with Ag-np treatment could be a better strategy to improve anti-proliferative effects in cancer cells. | |
dc.language.iso | en | |
dc.subject | DNA repair, DNA damage, silver nanoparticles and cancer therapy | |
dc.type | Thesis | |
dc.contributor.department | PHYSIOLOGY | |
dc.contributor.supervisor | MANOOR PRAKASH HANDE | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY | |
dc.identifier.isiut | NOT_IN_WOS | |
Appears in Collections: | Ph.D Theses (Open) |
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PhD_Thesis_2013-Hui_Kheng_LIM.pdf | 3.19 MB | Adobe PDF | OPEN | None | View/Download |
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