RT Journal Article
SR Electronic
T1 Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2315
OP 2322
VO 37
IS 5
A1 YI, ZHANG
A1 YAN, ZHAO
A1 MIYAHARA, KAZUMA
A1 SHIMADA, MAI
A1 TANAKA, KEN-ICHI
A1 HAYASHI, HIROYUKI
A1 IHARA, NORIKO
A1 MUROHASHI, IKUO
YR 2017
UL http://ar.iiarjournals.org/content/37/5/2315.abstract
AB 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.