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- Title
Vanadyl bisacetylacetonate induced G1/S cell cycle arrest via high-intensity ERK phosphorylation in HepG2 cells.
- Authors
Ying Fu; Qin Wang; Xiao-Gai Yang; Xiao-Da Yang; Kui Wang
- Abstract
In recent years the anticancer properties of vanadium compounds have been noticed, but the underlying mechanisms are not well understood. In the present work, we found that vanadyl bisacetylacetonate ([VO(acac)2]) blocked cell cycle progression permanently at G1 phase in a dose- and time-dependent manner in HepG2 cells. This was further evidenced by the growth regulatory signals during the G1 stage. After the treatment with [VO(acac)2], the level of phophorylation of retinoblastoma tumor suppressor protein (pRb) and the expressions of cyclin D1, cyclin E and cyclin A were reduced, while the expression of a cyclin-dependent kinase inhibitor p21 was increased dose-dependently. In the meantime, neither O2•− nor H2O2 level was observed to increase. Interestingly, the levels of phosphorylated extracellular signal-regulated protein kinase (ERK) and Akt were highly activated. After 1-h pretreatment with a lower concentration of MEK inhibitor U0126, the level of phosphorylated pRb was restored, indicating a release of cell cycle arrest. Taken together, we suggested that [VO(acac)2]-induced proliferation inhibition was caused by G1/S cell cycle arrest, which resulted from the decreased level of phosphorylated pRb in its active hypophosphorylated form via a highly activated ERK signal in HepG2 cells. The results presented here provided new insight into the development of vanadium compounds as potential anticancer agents.
- Subjects
CELL cycle; RETINOBLASTOMA; PHOSPHORYLATION; PROTEIN kinases; VANADIUM; ANTINEOPLASTIC agents
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2008, Vol 13, Issue 6, p1001
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-008-0387-2