Antimycin A as a mitochondria damage agent induces an S phase arrest of the cell cycle in HeLa cells.
Antimycin A (AMA), an electron transport chain inhibitor in mitochondria can produce reactive oxygen species (ROS) in cells. It has been reported that ROS may have roles in cell cycle progression via regulating cell cycle-related proteins. In the present study, we investigated the changes of the cell cycle distribution in AMA-treated HeLa cells in relation to cell cycle-related proteins. DNA flow cytometric analysis indicated that treatment with AMA significantly induced an S phase arrest of the cell cycle at 72 h. AMA decreased the expression of cyclin-dependent kinase inhibitor (CDKI), p21 and p27, CDK4, and cdc2 proteins. The expression of CDK6, cyclin D1, cyclin E, cyclin A, and cyclin B proteins was increased by 0.5 microM AMA, but was decreased by 2 and 10 microM AMA. The phosphorylation of Rb on the Ser (780) residue was increased by 0.5 microM AMA. Furthermore, treatment with AMA caused the accumulation of cells expressing cyclin A, B, and D1 proteins at the S phase of the cell cycle. However, treatment with 100 microM AMA nonspecifically extended all phases of the cell cycle. In conclusion, treatment with AMA (2, 10 and 50 microM) induced an S phase arrest of the cell cycle. An S phase arrest was accompanied by the alteration of other cell cycle-regulated proteins as well as S phase-related proteins.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Centers for Healthcare Technology Development, Chonbuk National University, JeonJu, Republic of Korea.
Kim
Suhn Hee
SH
Kim
Sung Zoo
SZ
Park
Woo Hyun
WH
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D017382:Reactive Oxygen Species; D016196:S Phase / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D016213:Cyclins; D017382:Reactive Oxygen Species; D000968:Antimycin A