title: The effects of 56MESS on mitochondrial and cytoskeletal proteins and the cell cycle in MDCK cells.
abstract: BACKGROUND
  56MESS has been shown to be cytotoxic but the mode of this action is unclear. In order to probe the mechanism of action for 56MESS, MDCK cells were utilised to investigate the effect on treated cells.
  
  
  RESULTS
  IC50 values for 56MESS and cisplatin in the MDCK cell line, determined by a SRB assay, were 0.25 ± 0.03 and 18 ± 1.2 μM respectively. In a preliminary study, cells treated with 56MESS displayed no caspase-3/7 activity, suggesting that the mechanism of action is caspase independent. Protein expression studies revealed an increase the expression in the MTC02 protein associated with mitochondria in cells treated with 56MESS and cisplatin. Non-synchronised 56MESS-treated cells caused an arrest in the G2/M phase of the cell cycle, in comparison to the S phase arrest of cisplatin. In G0/G1 synchronised cells, both 56MESS and cisplatin both appeared to arrest within the S phase.
  
  
  CONCLUSIONS
  these results suggest that 56MESS is capable of causing cell-cycle arrest, and that mitochondrial and cell cycle proteins may be involved in the mode of action of cytotoxicity of 56MESS.
authors.affiliation: Nanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW. 2751, Australia.
authors.forename: K Benjamin
authors.initials: KB
authors.lastname: Garbutcheon-Singh
authors.forename: Simon
authors.initials: S
authors.lastname: Myers
authors.forename: Benjamin W J
authors.initials: BW
authors.lastname: Harper
authors.forename: Neville S
authors.initials: NS
authors.lastname: Ng
authors.forename: Qihan
authors.initials: Q
authors.lastname: Dong
authors.forename: Chanlu
authors.initials: C
authors.lastname: Xie
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002945:Cisplatin / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D008928:Mitochondria / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000737:chemistry*; D017671:Platinum Compounds / Q000737:chemistry*; D013997:Time Factors
chemical_list: C539772:(1,2-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)platinum(II); D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D024101:Mitochondrial Proteins; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D053148:Caspase 3; D053179:Caspase 7; D002945:Cisplatin