ArticleMolecular pharmacology2010
Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence.Nature communications · 2025Article
- Reprogramming tumor immune microenvironment by milbemycin oxime results in pancreatic tumor growth suppression and enhanced anti-PD-1 efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness.Science advances · 2023Article
- Baicalein Induces GMolecules (Basel, Switzerland) · 2023Article
- Review
- GABAMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Anti-tumor effects ofHeliyon · 2020Article
- 3,3'-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species.Pharmaceutical biology · 2018Article
- Loss of MutL Disrupts CHK2-Dependent Cell-Cycle Control through CDK4/6 to Promote Intrinsic Endocrine Therapy Resistance in Primary Breast Cancer.Cancer discovery · 2017Article
- Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication.Virology journal · 2015Article
- Unfolded protein response mediated JNK/AP-1 signal transduction, a target for ovarian cancer treatment.International journal of clinical and experimental pathology · 2015Article
- Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.PloS one · 2014Article
- Apoptosis signal-regulating kinase 1-thioredoxin complex dissociation by capsaicin causes pancreatic tumor growth suppression by inducing apoptosis.Antioxidants & redox signaling · 2012Article
- Diindolylmethane-mediated Gli1 protein suppression induces anoikis in ovarian cancer cells in vitro and blocks tumor formation ability in vivo.The Journal of biological chemistry · 2012Article
- Natural compounds as anticancer agents: Experimental evidence.World journal of experimental medicine · 2012Review
- Regulation of macroautophagy in ovarian cancer cells in vitro and in vivo by controlling glucose regulatory protein 78 and AMPK.Oncotarget · 2012Article
- Blocking epidermal growth factor receptor activation by 3,3'-diindolylmethane suppresses ovarian tumor growth in vitro and in vivo.The Journal of pharmacology and experimental therapeutics · 2012Article
- Article
- Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro and in preclinical mouse model.PloS one · 2012Article
- RETRACTED: Mechanisms and therapeutic implications of cell death induction by indole compounds.Cancers · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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 establish the involvement of Chk2 in DIM-mediated G(2)/M arrest, cells were transfected with dominant-negative Chk2 (DN-Chk2). Blocking Chk2 activation by DN-Chk2 completely protected cells from DIM-mediated G(2)/M arrest. These results were further confirmed in Chk2 knockout DT40 lymphoma cells, in which DIM failed to cause cell cycle arrest. These results clearly indicate the requirement of Chk2 activation to cause G(2)/M arrest by DIM in ovarian cancer cells. Moreover, blocking Chk2 activation also abrogates the apoptosis-inducing effects of DIM. Furthermore, our results show that DIM treatment cause ROS generation. Blocking ROS generation by N-acetyl cysteine protects the cells from DIM-mediated G(2)/M arrest and apoptosis. Our results establish Chk2 as a potent molecular target of DIM in ovarian cancer cells and provide the rationale for further clinical investigation of DIM.
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