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Salvianolic acid A, a novel PI3K/Akt inhibitor, induces cell apoptosis and suppresses tumor growth in acute myeloid leukemia.
- Source :
-
Leukemia & lymphoma [Leuk Lymphoma] 2018 Aug; Vol. 59 (8), pp. 1959-1967. Date of Electronic Publication: 2017 Nov 22. - Publication Year :
- 2018
-
Abstract
- Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML.
- Subjects :
- Animals
Cell Line, Tumor
Female
Humans
Leukemia, Myeloid, Acute pathology
Male
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
THP-1 Cells
Tumor Burden drug effects
Apoptosis drug effects
Caffeic Acids pharmacology
Lactates pharmacology
Leukemia, Myeloid, Acute drug therapy
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Xenograft Model Antitumor Assays
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2403
- Volume :
- 59
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Leukemia & lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 29164984
- Full Text :
- https://doi.org/10.1080/10428194.2017.1399314