title: Investigation of cell cycle arrest effects of actinomycin D at G1 phase using proteomic methods in B104-1-1 cells.
abstract: Actinomycin D was previously reported as an inhibitor of Shc/Grb2 interaction in B104-1-1 cells. Actinomycin D arrested the cell cycle at the G1 phase at 1nM, which is about 10 times lower than the inhibition of Shc/Grb2 interactions in B104-1-1 cells. To evaluate other mechanisms of actinomycin D affected suppression of tumors and cell growth, except inhibition of Shc/Grb2 interactions, we examined the proteomic expression profile by proteomic technology. We found up-regulation of MEKK3 and down-regulation of Hsp70 expression from proteomic analysis, which is a very interesting observation because MEKK3 is strongly related with G1 arrest of cell cycle and Hsp70 is also involved in cell cycle regulation. These results indicate that the anti-tumor effects of actinomycin D is due to synergic effects of various proteins regulated by the compound including inhibition of the Shc/Grb2 interaction and other signaling pathways in the cytoplasm. Here we provide a mechanism-based explanation for growth inhibition by actinomycin D using proteomic technology. Thus, this approach may be a potentially useful method to reveal new mechanisms of active compounds or drugs with unknown cellular function.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Taejon.
authors.forename: Hyae-Kyeong
authors.initials: HK
authors.lastname: Kim
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kong
authors.forename: Moon-Jin
authors.initials: MJ
authors.lastname: Jeong
authors.forename: Dong-Cho
authors.initials: DC
authors.lastname: Han
authors.forename: Jung-Do
authors.initials: JD
authors.lastname: Choi
authors.forename: Hak-Yong
authors.initials: HY
authors.lastname: Kim
authors.forename: Kab-Seok
authors.initials: KS
authors.lastname: Yoon
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Son
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D051379:Mice; D041681:NIH 3T3 Cells; D040901:Proteomics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D003609:Dactinomycin; D018719:Erb-b2 Receptor Tyrosine Kinases