scholarly journals Cordycepin induces apoptosis of human acute monocytic leukemia cells via downregulation of the ERK/Akt signaling pathway

2017 ◽  
Vol 14 (4) ◽  
pp. 3067-3073 ◽  
Author(s):  
Yue Wang ◽  
Huimin Mo ◽  
Jun Gu ◽  
Kan Chen ◽  
Zhihua Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Leukemia Cells ◽  
Acute Monocytic Leukemia ◽  
Akt Signaling Pathway ◽  
Monocytic Leukemia

scholarly journals Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells

2019 ◽  
Vol 9 (3) ◽  
pp. 470-480 ◽  
Author(s):  
Elahe Naderali ◽  
Behnaz Valipour ◽  
Amir Afshin Khaki ◽  
Jafar Soleymani Rad ◽  
Alireza Alihemmati ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Akt Signaling ◽  
Leukemia Cells ◽  
Akt Signaling Pathway ◽  
Inhibition Of Proliferation ◽  
Positive Effects ◽  
P53 Mrna

Purpose: The PI3K/Akt signaling pathway regulates cell growth, proliferation and viability in hematopoietic cells. This pathway always dysregulates in acute lymphoblastic leukemia (ALL). PTEN and P53 are tumor suppressor genes correlated with PI3K/Akt signaling pathway, and both have a tight link in regulation of cell proliferation and cell death. In this study, we investigated the effects of dual targeting of PI3K/Akt pathway by combined inhibition with nvp-BKM-120 (PI3K inhibitor) and MK-2206 (Akt inhibitor) in relation with PTEN and P53 on apoptosis and proliferation of leukemia cells. Methods: Both T and B ALL cell lines were treated with both inhibitors alone or in combination with each other, and induction of apoptosis and inhibition of proliferation were evaluated by flow cytometry. Expression levels of PTEN as well as p53 mRNA and protein were measured by real-time qRT-PCR and western blot, respectively. Results: We indicated that both inhibitors (BKM-120 and MK-2206) decreased cell viability and increased cytotoxicity in leukemia cells. Reduction in Akt phosphorylation increased PTEN and p53 mRNA and p53 protein level (in PTEN positive versus PTEN negative cell lines). Additionally, both inhibitors, particularly in combination with each other, increased apoptosis (evaluated with Annexin V and caspase 3) and reduced proliferation (Ki67 expression) in leukemia cells. However, administration of IL7 downregulated PTEN and P53 mRNA expression and rescued cancer cells following inhibition of BKM-120 and MK-2206. Conclusion: This investigation suggested that inhibition of Akt and PI3K could be helpful in leukemia treatment.

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