Cell cycle checkpoints and their inactivation in human cancer

Molinari, Marta

doi:10.1046/j.1365-2184.2000.00191.x

Cited by 329 publications

(281 citation statements)

References 124 publications

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“…17) The control of cell-cycle progression in cancer cells is considered an effective strategy to prevent or delay tumor growth. 18,19) This assumption is based on a molecular analysis of human cancer, wherein cell cycle regulators are frequently de-regulated in most of the common malignancies. 20,21) Despite recent advancement in understanding the carcinogenic process of PCA, the increasing incidence and relatively low remission rate of chemotherapy have prompted the scientific community to establish more effective treatment regimens by adopting novel and innovative approaches.…”

Section: Discussionmentioning

confidence: 99%

Fangchinoline Induced G1/S Arrest by Modulating Expression of p27, PCNA, and Cyclin D in Human Prostate Carcinoma Cancer PC3 Cells and Tumor Xenograft

Wang

Huang

Gao

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

Fangchinoline Induced G1/S Arrest by Modulating Expression of p27, PCNA, and Cyclin D in Human Prostate Carcinoma Cancer PC3 Cells and Tumor Xenograft

Wang

Huang

Gao

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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“…However, cell cycle arrest at the G2/M checkpoint is a critical component of stress response, allowing DNA damage repair (Kaufmann, 1995;Molinari, 2000;Stark and Taylor, 2006). Moreover, deficiencies in the G2/M phase checkpoint control are often associated with genomic instability and tumorigenesis (Lobrich and Jeggo, 2007).…”

Section: Foxo and The G1/s Phase Transitionmentioning

confidence: 99%

Many forks in the path: cycling with FoxO

2008

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FoxO transcription factors are an evolutionary conserved subfamily of the forkhead transcription factors, characterized by the forkhead DNA-binding domain. FoxO factors regulate a number of cellular processes involved in cell-fate decisions in a cell-type-and environment-specific manner, including metabolism, differentiation, apoptosis and proliferation. A key mechanism by which FoxO determines cell fate is through regulation of the cell cycle machinery, and as such the cellular consequence of FoxO deregulation is often manifested through perturbation of the cell cycle. Consequently, the deregulation of FoxO factors is implicated in the development of numerous proliferative diseases, in particular cancer.

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“…Curcumin treatment modulates expression of G2/M cell cycle regulatory proteins DNA damage generally leads to the activation of the ATM/ATR pathway (Molinari, 2000;Abraham, 2001;Lukas et al, 2001;Huang et al, 2008). To further delineate the molecular mechanism of curcumin-mediated G2/M arrest, we determine its effect on the key-signaling proteins of this pathway.…”

Section: Curcumin Causes Dna Damage and Induces Apoptosismentioning

confidence: 99%

“…(Singh and Khar, 2006;Tse et al, 2007). During DNA damage, cells are blocked in G2/M phase to provide time to repair damaged DNA (Molinari, 2000;Abraham, 2001), or lead to apoptotic cell death in case of severe DNA damage . Several studies have indicated that curcumin induces cell cycle arrest and apoptosis in various human cancer cells (Park et al, 2006;Tan et al, 2006;Srivastava et al, 2007;Weir et al, 2007;Lin et al, 2008;Mackenzie et al, 2008;Sun et al, 2008).…”

Section: Curcumin Causes Dna Damage and Induces Apoptosismentioning

confidence: 99%

Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells

2009

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Curcumin has been shown to inhibit the growth of various types of cancer cells; however, at concentrations much above the clinically achievable levels in humans. The concentration of curcumin achieved in the plasma after oral administration in humans was estimated to be around 1.8 mM. Here, we report that treatment of BxPC-3 human pancreatic cancer cells with a low and single exposure of 2.5 mM curcumin for 24 h causes significant arrest of cells in the G2/M phase and induces significant apoptosis. Immunoblot studies revealed increased phosphorylation of H2A.X at Ser-139 and Chk1 at Ser-280 and a decrease in DNA polymerase-b level in curcumin-treated cells. Phosphorylation of H2A.X and Chk1 proteins are an indicator of DNA damage whereas DNA polymerase-b plays a role in the repair of DNA strand breaks. Normal immortalised human pancreatic ductal epithelial (HPDE-6) cells remained unaffected by curcumin treatment. In addition, we also observed a significant increase in the phosphorylation of Chk1 at Ser-345, Cdc25C at Ser-216 and a subtle increase in ATM phosphorylation at Ser-1981. Concomitant decrease in the expressions of cyclin B1 and Cdk1 were seen in curcumin-treated cells. Further, curcumin treatment caused significant cleavage of caspase-3 and PARP in BxPC-3 but not in HPDE-6 cells. Silencing ATM/Chk1 expression by transfecting BxPC-3 cells with ATM or Chk1-specific SiRNA blocked the phosphorylation of ATM, Chk1 and Cdc25C and protected the cells from curcumin-mediated G2/M arrest and apoptosis. This study reflects the critical role of ATM/Chk1 in curcumin-mediated G2/M cell cycle arrest and apoptosis in pancreatic cancer cells.

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Cell cycle checkpoints and their inactivation in human cancer

Cited by 329 publications

References 124 publications

Fangchinoline Induced G1/S Arrest by Modulating Expression of p27, PCNA, and Cyclin D in Human Prostate Carcinoma Cancer PC3 Cells and Tumor Xenograft

Fangchinoline Induced G1/S Arrest by Modulating Expression of p27, PCNA, and Cyclin D in Human Prostate Carcinoma Cancer PC3 Cells and Tumor Xenograft

Many forks in the path: cycling with FoxO

Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells

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