Oligosaccharide-linked acyl carrier protein, a novel transmethylase inhibitor, from porcine liver inhibits cell growth.
We have previously reported on the identification of the endogenous transmethylation inhibitor oligosaccharide-linked acyl carrier protein (O-ACP). In this study, the role of the transmethylation reaction on cell cycle progression was evaluated using various transmethylase inhibitors, including O-ACP. O-ACP significantly inhibited the growth of various cancer cell lines, including NIH3T3, ras-transformed NIH3T3, MDA-MB-231, HT-1376, and AGS. In addition, exposure of ras-transformed NIH3T3 to O-ACP caused cell cycle arrest at the G0/G1 phase, which led to a decrease in cells at the S phase, as determined by flow cytometry. In contrast, transmethylase inhibitors did not affect the expression of p21(WAF1/Cip1), a well known inhibitor of cyclin dependent kinase, indicating that the cell cycle arrest by transmethylase inhibitors might be mediated by a p21(WAF1/Cip1)-independent mechanism. Therefore, O-ACP, a novel transmethylase inhibitor, could be a useful tool for elucidating the novel role of methylation in cell proliferation and cell cycle progression.
Seo
Dong Wan
DW
Kim
Yong Kee
YK
Cho
Eun-Jung
EJ
Han
Jeung-Whan
JW
Lee
Hoi Young
HY
Hong
Sungyoul
S
Lee
Hyang-Woo
HW
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D051379:Mice; D009844:Oligosaccharides / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
C493956:CDKN1A protein, human; D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D004247:DNA; D008156:Luciferases; D008780:Methyltransferases; D013936:Thymidine