title: The selective cytotoxicity of DSF-Cu attributes to the biomechanical properties and cytoskeleton rearrangements in the normal and cancerous nasopharyngeal epithelial cells.
abstract: Cancer initiation and progression follow complex changes of cellular architecture and biomechanical property. Cancer cells with more submissive (or "softer") than their healthy counterparts attributed to the reorganization of the complex cytoskeleton structure, may be considered as a potential anti-tumor therapeutic target. In this study, atomic force microscopy (AFM) was carried out to detect the topographical and biophysical changes of nasopharyngeal carcinoma CNE-2Z cells and normal nasopharyngeal epithelial cells NP69-SV40T by treating the Disulfiram chelated with Cu2+(DSF-Cu). DSF-Cu induced the apoptotic population, ROS production and decreased the NF-κB-p65 expression of CNE-2Z cells, which was much higher than those of NP69-SV40T cells. DSF-Cu caused the obvious changes of cell morphology and membrane ultrastructure in CNE-2Z cells. The roughness decreased and stiffness increased significantly in CNE-2Z cells, which correlated with the rearrangement of intracellular F-actin, FLNa and α-tubulin structures in CNE-2Z cells. And the adhesion force of CNE-2Z cells was also increased accompanied with the increased E-cadherin expression. However, these results could not be observed in the NP69-SV40T cells even the concentration of DSF reached up to 400nM. Finally, the detection of cell wound scratch assay confirmed DSF-Cu could inhibit the migration of CNE-2Z cells, but no effect on NP69-SV40T cells. These findings demonstrated the selective cytotoxicity of DSF-Cu in CNE-2Z cells may attribute to the different mechanical properties and cytoskeleton rearrangement from the normal nasopharyngeal epithelial cells.
authors.affiliation: Analysis and Test Center, Jinan University, Guangzhou 510632, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China; Institute of Clinical Pharmacy, Beijing Municipal Health Bureau, Beijing 100035, China.
authors.forename: Mengjia
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Congran
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Analysis and Test Center, Jinan University, Guangzhou 510632, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: linyanzhu_jnu@163.com.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China. Electronic address: yang_hf@126.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001696:Biomechanical Phenomena; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004221:Disulfiram / Q000031:analogs & derivatives* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D064448:Filamins / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009305:Nasopharynx / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; C578663:FLNA protein, human; D064448:Filamins; C498143:RELA protein, human; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014404:Tubulin; D004221:Disulfiram
keywords: Adhesion force; Atomic force microscopy; Cell stiffness; Cytoskeletal reorganization; Nasopharyngeal carcinoma cells