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Hematology. 2012 Jul;17(4):198-206. doi: 10.1179/1607845412Y.0000000008.

Cytotoxic effect of arsenic trioxide on acute promyelocytic leukemia cells through suppression of NFkβ-dependent induction of hTERT due to down-regulation of Pin1 transcription.

Author information

  • 1Department of Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. shghaffari200@yahoo.com

Abstract

Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contributes to the morbidity and mortality of the disease. This study was purposed to dissect the molecular mechanisms underlying telomerase-dependent arsenic trioxide (ATO)-induced cytotoxic and anti-proliferative effects in NB4 cells. ATO exposure was associated with transcriptional repression of Pin1, survivin, c-Myc, hTERT, and PinX1 along with an expressive enhancement in p73 mRNA level. Moreover, ATO treatment suppressed cell growth, viability and metabolic activity, exerted apoptosis, hindered telomerase activity, shortened telomere length, and dampened NF-κB activation. On aggregate, these issues indicate that ATO might preempt cell growth and proliferation in NB4 cells through suppression of Pin1-mediated NF-κB-dependent stimulation of telomerase and survivin.

PMID:
22944098
[PubMed - indexed for MEDLINE]
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