Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells.

ABSTRACT: We evaluated the effect of 3,3'-diindolylmethane (DIM) in ovarian cancer cells. DIM treatment inhibited the growth of SKOV-3, TOV-21G, and OVCAR-3 ovarian cancer cells in both a dose- and time-dependent manner with effective concentrations ranging from 40 to 100 muM. Growth-inhibitory effects of DIM were mediated by cell cycle arrest in G(2)/M phase in all the three cell lines. G(2)/M arrest was associated with DNA damage as indicated by phosphorylation of H(2)A.X at Ser139 and activation of checkpoint kinase 2 (Chk2) in all the three cell lines. Other G(2)/M regulatory molecules such as Cdc25C, Cdk1, cyclin B1 were down-regulated by DIM. Cycloheximide or Chk2 inhibitor pretreatment abrogated not only activation of Chk2 but also G(2)/M arrest and apoptosis mediated by DIM. To further estab

SUBMITTER: Kandala PK 

PROVIDER: S-EPMC2917853 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature