2005
DOI: 10.1182/blood-2005-03-1263
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Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation

Abstract: Iron is critical for cell growth and proliferation. Iron chelators are being explored for a number of clinical applications, including the treatment of neurodegenerative disorders, heart disease, and cancer. To uncover mechanisms of action of tachpyridine, a chelator currently undergoing preclinical evaluation as an anticancer agent, cell-cycle analysis was performed. Tachpyridine arrested cells at G 2 , a radiosensitive phase of the cell cycle, and enhanced the sensitivity of cancer cells but not nontransform… Show more

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Cited by 69 publications
(66 citation statements)
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“…In fact, radiation increased the sensitivity of tumor cells to the action of tachpyridine (41). This result was unexpected because most Fe chelators arrest cells at the G 1 -S interface due to inhibition of ribonucleotide reductase (16).…”
Section: New-generation Lipophilic Fe Chelatorsmentioning
confidence: 77%
See 2 more Smart Citations
“…In fact, radiation increased the sensitivity of tumor cells to the action of tachpyridine (41). This result was unexpected because most Fe chelators arrest cells at the G 1 -S interface due to inhibition of ribonucleotide reductase (16).…”
Section: New-generation Lipophilic Fe Chelatorsmentioning
confidence: 77%
“…Interestingly, tachpyridine arrests cells at G 2 , which is a radiosensitive phase of the cell cycle (41). In fact, radiation increased the sensitivity of tumor cells to the action of tachpyridine (41).…”
Section: New-generation Lipophilic Fe Chelatorsmentioning
confidence: 99%
See 1 more Smart Citation
“…87 A structurally different ligand known as Tachpyridine is also currently in pre-clinical development with the National Cancer Institute. 88 Another series of chelators are those of the PIH class that led to the development of the highly permeable ligand, 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311). 79,89 This compound shows much greater Fe chelation efficacy and anti-tumor activity than DFO.…”
Section: Iron As Possible Therapeutic Strategy For Cancer Treatmentmentioning
confidence: 99%
“…Cancer cells show increased uptake and utilization of iron by virtue of possessing significantly higher levels of transferrin receptor 1 than healthy cells (10). These unique characteristics of neoplastic cells have been exploited recently by the use of iron chelators that show significant antitumor activity in vitro and in animal models (11,12). Targeting iron metabolism has resulted in compounds with some antitumor activity such as desferrioxamine (desferal or desferrioxamine; refs.…”
Section: Introductionmentioning
confidence: 99%