Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia
Author
Alameen, Ayman A.M.; Simioni, Carolina; Martelli, Alberto; Zauli, Giorgio; Ultimo, Simona; McCubrey, James A.; Gonelli, Arianna; Marisi, Giorgia; Ulivi, Paola; Capitani, Silvano; Neri, Luca
Abstract
An attractive molecular target for novel anti-cancer therapies is the
phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
pathway which is commonly deregulated in many types of cancer. Nevertheless, the
effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune
responses, have been seldom explored. In this study we investigated the effects on
human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T
cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor effects
on cell cycle and apoptosis were analyzed by flow cytometry, while cytotoxicity was
assessed by MTT assays. In addition, the activation status of the pathway as well as
induction of autophagy were analyzed by Western blotting.
Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogenstimulated lymphocytes as well as leukemic cell lines displayed a cell cycle block,
caspase-dependent apoptosis, and dephosphorylation of key components of the
signaling pathway. Autophagy was also induced in proliferating lymphocytes and in
JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3-methyladenine
or Bafilomycin A1, drug cytotoxicity was increased, indicating that autophagy is a
protective mechanism.
Therefore, our findings suggest that PI3K/Akt/mTOR inhibitors preserve
lymphocyte viability. This is a valuable result to be taken into account when selecting
drugs for targeted cancer therapy in order to minimize detrimental effects on immune
function.
Date
2016-08-01
Citation:
APA:
Alameen, Ayman A.M., & Simioni, Carolina, & Martelli, Alberto, & Zauli, Giorgio, & Ultimo, Simona, & McCubrey, James A., & Gonelli, Arianna, & Marisi, Giorgia, & Ulivi, Paola, & Capitani, Silvano, & Neri, Luca. (August 2016).
Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8316
MLA:
Alameen, Ayman A.M., and Simioni, Carolina, and Martelli, Alberto, and Zauli, Giorgio, and Ultimo, Simona, and McCubrey, James A., and Gonelli, Arianna, and Marisi, Giorgia, and Ulivi, Paola, and Capitani, Silvano, and Neri, Luca.
"Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia". .
. (),
August 2016.
September 21, 2023.
http://hdl.handle.net/10342/8316.
Chicago:
Alameen, Ayman A.M. and Simioni, Carolina and Martelli, Alberto and Zauli, Giorgio and Ultimo, Simona and McCubrey, James A. and Gonelli, Arianna and Marisi, Giorgia and Ulivi, Paola and Capitani, Silvano and Neri, Luca,
"Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia," , no.
(August 2016),
http://hdl.handle.net/10342/8316 (accessed
September 21, 2023).
AMA:
Alameen, Ayman A.M., Simioni, Carolina, Martelli, Alberto, Zauli, Giorgio, Ultimo, Simona, McCubrey, James A., Gonelli, Arianna, Marisi, Giorgia, Ulivi, Paola, Capitani, Silvano, Neri, Luca.
Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia. .
August 2016;
():
.
http://hdl.handle.net/10342/8316. Accessed
September 21, 2023.
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