DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green exposure are associated with elevated phosphorylation of ERK1 and JNK1

Bose, Bipasha; Motiwale, Leena; Rao, K. Venkata

doi:10.1016/j.canlet.2005.01.001

Cited by 48 publications

(37 citation statements)

References 33 publications

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“…Our studies further show that DIM causes DNA double-strand breaks, suggesting that DIM-mediated G 2 /M in our model is due to the DNA damage incurred by DIM. This is consistent with several other studies, including ours, showing a correlation between DNA damage and G 2 /M arrest (Bose et al, 2005;Zhang et al, 2006). However, the exact mechanism by which DIM causes DNA damage was not clear.…”

Section: Discussionsupporting

confidence: 92%

Activation of Checkpoint Kinase 2 by 3,3′-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells

Kandala¹,

Srivastava

2010

Molecular Pharmacology

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We evaluated the effect of 3,3Ј-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 doseand time-dependent manner with effective concentrations ranging from 40 to 100 M. 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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Section: Discussionsupporting

confidence: 92%

Activation of Checkpoint Kinase 2 by 3,3′-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells

Kandala¹,

Srivastava

2010

Molecular Pharmacology

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“…It is known that G 1 /S and G 2 /M check-point controls prevent the acquisition of multiple genetic changes by ensuring that DNA is repaired before replication in S-phase and appropriately segregated during M phase of the cell cycle, respectively. Incompletely replicated and damaged DNA generally signals arrest at G 2 /M in order to prevent mutations, translocation or chromosomal loss (18). Our results presented in Fig.…”

Section: Discussionsupporting

confidence: 65%

Differential effects of MAPKs signaling on the growth of invasive bladder cancer cells

Kumar¹,

Sinclair²,

Khandrika³

et al. 2009

Int J Oncol

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Abstract. Transitional cell carcinoma (TCC) is the most common form of bladder cancer. In bladder cancer, which in terms of its origins and genetics, is a representative of invasive tumors, the differing clinical course and the limited value of established prognostic markers compelled many researchers to look for new molecular parameters in predicting the prognosis and treatment of patients with bladder cancer. Activation of mitogen activated protein kinase (MAPK) is a frequent event in tumor progression and metastasis. In the current study, we investigated the role of two different MAPKs (ERK1/2 and p38) by using their specific inhibitors PD98059 and SB203580 respectively, on bladder cancer growth in two cell lines derived from different tumor stages. Our preliminary work showed that ERK1/2 and p38 MAP kinase are active during the log phase growth of bladder cancer, and inhibition of these pathways could reduce proliferation and growth. Moreover, treatment with these inhibitors hinders DNA synthesis, and has differential effects on the progression of cell cycle. ERK1/2 inhibitor caused cyclin B1-dependent G 2 /M arrest in both HTB5 and HTB9 bladder cancer cell lines, where as p38 MAPK inhibitor showed G 2 /M arrest in HTB9 and G 1 arrest in HTB5 cell line. Furthermore, decreased proliferation and growth arrest caused by MAPK inhibitors was found to be a reflection of apoptotic induction by these inhibitors in bladder cancer cells. Thus, these studies establish MAPKs as a molecular target in bladder cancer growth which could provide new molecular modalities in clinical application.

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“…It is soluble and stable in water at high concentrations. While it is toxic to mammalian cells (Bose et al, 2004(Bose et al, , 2005Fessard et al, 1999;Gupta et al, 2003;Littlefield et al, 1985;Stammati et al, 2005), several species of fungi and bacteria are known to decolorize and degrade malachite green through a variety of pathways.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

2007

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DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green exposure are associated with elevated phosphorylation of ERK1 and JNK1

Cited by 48 publications

References 33 publications

Activation of Checkpoint Kinase 2 by 3,3′-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells

Activation of Checkpoint Kinase 2 by 3,3′-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells

Differential effects of MAPKs signaling on the growth of invasive bladder cancer cells

Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

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