Investigation of cell cycle arrest effects of actinomycin D at G1 phase using proteomic methods in B104-1-1 cells.
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.
Kim
Hyae-Kyeong
HK
Korea Research Institute of Bioscience and Biotechnology, Taejon.
Kong
Mi-Young
MY
Jeong
Moon-Jin
MJ
Han
Dong-Cho
DC
Choi
Jung-Do
JD
Kim
Hak-Yong
HY
Yoon
Kab-Seok
KS
Kim
Jung-Min
JM
Son
Kwang-Hee
KH
Kwon
Byoung-Mog
BM
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
D015415:Biomarkers; D003609:Dactinomycin; D018719:Erb-b2 Receptor Tyrosine Kinases