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Research ArticleExperimental Studies

Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies

ZHANG YI, ZHAO YAN, KAZUMA MIYAHARA, MAI SHIMADA, KEN-ICHI TANAKA, HIROYUKI HAYASHI, NORIKO IHARA and IKUO MUROHASHI
Anticancer Research May 2017, 37 (5) 2315-2322;
ZHANG YI
1Hematology, Center for University-Wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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ZHAO YAN
1Hematology, Center for University-Wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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KAZUMA MIYAHARA
2Department of Health Sciences, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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MAI SHIMADA
2Department of Health Sciences, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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KEN-ICHI TANAKA
3Physiology, Center for University-Wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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HIROYUKI HAYASHI
4Anatomy, Center for University-Wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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NORIKO IHARA
2Department of Health Sciences, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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IKUO MUROHASHI
1Hematology, Center for University-Wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan
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  • For correspondence: murohashi-ikuo@spu.ac.jp
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Abstract

Background: With our newly established long-term suspension culture, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the self-renewal capacity of blast progenitors in seven hematological malignant cell lines. Materials and Methods: Cyclo-oxygenase inhibitors NS-398 (NS) or indomethacin heptyl ester (indomethacin) at 30 μM was added to the cell culture. In U-937 cells, indomethacin was added at 0.3 or 3 μM. Results: In all cell lines, the agents significantly and markedly inhibited blast colony formation (BCF) and telomerase activity, respectively. Significant exponential clonogenic cell growth was noted under all 23 conditions with or without the agent. The relative slope (SLP) of the line (SLPagent/SLPcontrol) reflects the level of self-renewal induced by the agent and self-renewal was inhibited (relative SLP at 0.9 or below) in four out of 16 conditions, including in U-937 cells treated with 0.3 or 3 μM indomethacin, in Daudi cells treated with indomethacin and in U-266 cells treated with NS. Indomethacin enhanced senescence, necrosis and apoptosis in U-937 and Daudi cells, whereas NS reduced apoptosis in U-937 cells and had no effect on senescence, necrosis and apoptosis in Daudi cells. In U-266 cells, NS enhanced senescence and necrosis, whereas indomethacin reduced apoptosis. There was no significant correlation between the control of BCF and relative SLP. Conclusion: NSAIDs enhance or reduce stress responses, inhibit telomerase activity and differentially regulate BCF and self-renewal.

  • NSAIDs
  • hematological malignancies
  • long-term suspension culture
  • self-renewal capacity
  • blast colony formation
  • terminal divisions
  • telomerase
  • Received February 21, 2017.
  • Revision received March 17, 2017.
  • Accepted March 31, 2017.
  • Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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Anticancer Research: 37 (5)
Anticancer Research
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May 2017
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Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies
ZHANG YI, ZHAO YAN, KAZUMA MIYAHARA, MAI SHIMADA, KEN-ICHI TANAKA, HIROYUKI HAYASHI, NORIKO IHARA, IKUO MUROHASHI
Anticancer Research May 2017, 37 (5) 2315-2322;

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Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies
ZHANG YI, ZHAO YAN, KAZUMA MIYAHARA, MAI SHIMADA, KEN-ICHI TANAKA, HIROYUKI HAYASHI, NORIKO IHARA, IKUO MUROHASHI
Anticancer Research May 2017, 37 (5) 2315-2322;
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Keywords

  • NSAIDs
  • hematological malignancies
  • long-term suspension culture
  • self-renewal capacity
  • blast colony formation
  • terminal divisions
  • telomerase
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