title: Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1.
abstract: Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione treatment in 6 h. Menadione did not have an influence on mRNA level of CDK1 and cyclin B1 though the protein levels were decreased. However, the decreased protein levels of CDK1 and cyclin B1 were recovered by inhibition of proteasome. Collectively, these results suggest that menadione inhibits growth of gastric cancer cells by reducing expression of CDC25C and promoting proteasome mediated degradation of CDK1 and cyclin B1 thereby blocking transition of the cell cycle from G2 phase to M phase.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Hyun Jun
authors.initials: HJ
authors.lastname: Woo
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Yeon
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Clinical Laboratory Science, Semyung University Jaecheon, Republic of Korea.
authors.forename: Sa-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Clinical Laboratory Science, Semyung University Jaecheon, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Moon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University Providence, Rhode Island, United States of America.
authors.forename: Nagendran
authors.initials: N
authors.lastname: Tharmalingam
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Tae Ue
authors.initials: TU
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Republic of Korea.
authors.forename: Jong-Bae
authors.initials: JB
authors.lastname: Kim
keywords: AGS; CDC25C; CDK1; Cyclin B1; G2/M arrest; Menadione