title: Vanadyl bisacetylacetonate induced G1/S cell cycle arrest via high-intensity ERK phosphorylation in HepG2 cells.
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 phosphorylation 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 O(2)(*-) nor H(2)O(2) 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.
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Gai
authors.initials: XG
authors.lastname: Yang
authors.forename: Xiao-Da
authors.initials: XD
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D010422:Pentanones / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology
chemical_list: D006885:Hydroxybutyrates; D010422:Pentanones; C049529:acetyl acetonate; D014638:Vanadates; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases