Inhibition of Mammalian Target of Rapamycin in Human Acute Myeloid Leukemia Cells Has Diverse Effects That Depend on the Environmental In Vitro Stress
Joint Authors
Paulsen Rye, Kristin
Ryningen, Anita
Reikvam, Håkon
Nepstad, Ina
Bruserud, Øystein
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-10-02
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Effects of the mTOR inhibitor rapamycin were characterized on in vitro cultured primary human acute myeloid leukemia (AML) cells and five AML cell lines.
Constitutive mTOR activation seemed to be a general characteristic of primary AML cells.
Increased cellular stress induced by serum deprivation increased both mTOR signaling, lysosomal acidity, and in vitro apoptosis, where lysosomal acidity/apoptosis were independent of increased mTOR signaling.
Rapamycin had antiproliferative and proapoptotic effects only for a subset of patients.
Proapoptotic effect was detected for AML cell lines only in the presence of serum.
Combination of rapamycin with valproic acid, all-trans retinoic acid (ATRA), and NF-κB inhibitors showed no interference with constitutive mTOR activation and mTOR inhibitory effect of rapamycin and no additional proapoptotic effect compared to rapamycin alone.
In contrast, dual inhibition of the PI3K-Akt-mTOR pathway by rapamycin plus a PI3K inhibitor induced new functional effects that did not simply reflect a summary of single drug effects.
To conclude, (i) pharmacological characterization of PI3K-Akt-mTOR inhibitors requires carefully standardized experimental models, (ii) rapamycin effects differ between patients, and (iii) combined targeting of different steps in this pathway should be further investigated whereas combination of rapamycin with valproic acid, ATRA, or NF-κB inhibitors seems less promising.
American Psychological Association (APA)
Ryningen, Anita& Reikvam, Håkon& Nepstad, Ina& Paulsen Rye, Kristin& Bruserud, Øystein. 2012. Inhibition of Mammalian Target of Rapamycin in Human Acute Myeloid Leukemia Cells Has Diverse Effects That Depend on the Environmental In Vitro Stress. Bone Marrow Research،Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-463978
Modern Language Association (MLA)
Ryningen, Anita…[et al.]. Inhibition of Mammalian Target of Rapamycin in Human Acute Myeloid Leukemia Cells Has Diverse Effects That Depend on the Environmental In Vitro Stress. Bone Marrow Research No. 2012 (2012), pp.1-10.
https://search.emarefa.net/detail/BIM-463978
American Medical Association (AMA)
Ryningen, Anita& Reikvam, Håkon& Nepstad, Ina& Paulsen Rye, Kristin& Bruserud, Øystein. Inhibition of Mammalian Target of Rapamycin in Human Acute Myeloid Leukemia Cells Has Diverse Effects That Depend on the Environmental In Vitro Stress. Bone Marrow Research. 2012. Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-463978
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-463978