scholarly journals STL1, a New AKT Inhibitor, Synergizes with Flavonoid Quercetin in Enhancing Cell Death in A Chronic Lymphocytic Leukemia Cell Line

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5810
Author(s):  
Carmen Cervellera ◽  
Maria Russo ◽  
Serena Dotolo ◽  
Angelo Facchiano ◽  
Gian Luigi Russo

Using a pharmacophore model based on the experimental structure of AKT-1, we recently identified the compound STL1 (ZINC2429155) as an allosteric inhibitor of AKT-1. STL1, was able to reduce Ser473 phosphorylation, thus inhibiting the PI3K/AKT pathway. Moreover, we demonstrated that the flavonoid quercetin downregulated the phosphorylated and active form of AKT. However, in this case, quercetin inhibited the PI3K/AKT pathway by directly binding the kinases CK2 and PI3K. In the present work, we investigated the antiproliferative effects of the co-treatment quercetin plus STL1 in HG-3 cells, derived from a patient affected by chronic lymphocytic leukemia. Quercetin and STL1 in the mono-treatment maintained the capacity to inhibit AKT phosphorylation on Ser473, but did not significantly reduce cell viability. On the contrary, they activated a protective form of autophagy. When the HG-3 cells were co-treated with quercetin and STL1, their association synergistically (combination index < 1) inhibited cell growth and induced apoptosis. The combined treatment caused the switch from protective to non-protective autophagy. This work demonstrated that cytotoxicity could be enhanced in a drug-resistant cell line by combining the effects of different inhibitors acting in concert on PI3K and AKT kinases.

2013 ◽  
Vol 8 (6) ◽  
pp. 1866-1870 ◽  
Author(s):  
XINYU LIU ◽  
XIANGLU LI ◽  
LING WANG ◽  
XIAO LV ◽  
NA CHEN ◽  
...  

1993 ◽  
Vol 17 (10) ◽  
pp. 883-894 ◽  
Author(s):  
Akira Kawata ◽  
Tin Han ◽  
Barbara Dadey ◽  
Heinz-Ulrich G. Weier ◽  
Morihiro Okazaki ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document