The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells

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http://hdl.handle.net/10138/300993

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Adem , J , Eray , M , Eeva , J , Nuutinen , U & Pelkonen , J 2018 , ' The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells ' , Leukemia Research , vol. 66 , pp. 57-65 . https://doi.org/10.1016/j.leukres.2018.01.015

Title: The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells
Author: Adem, Jemal; Eray, Mine; Eeva, Jonna; Nuutinen, Ulla; Pelkonen, Jukka
Contributor: University of Helsinki, HUSLAB
Date: 2018-03
Language: eng
Number of pages: 9
Belongs to series: Leukemia Research
ISSN: 0145-2126
URI: http://hdl.handle.net/10138/300993
Abstract: We have previously shown that the human follicular lymphoma cell line, HF28GFP, is sensitive to TRAIL-mediated apoptosis. Nevertheless, when the same cells overexpress anti-apoptotic Bcl-2 family protein, Bcl-xL (HF28Bcl-xL), they become resistant to TRAIL. Thus, these cell lines help us to investigate the action of novel apoptosis inducing candidate drugs. In the present study, we examined the effects of MG-132 (a proteasome inhibitor), LiCl (a glycogen synthase kinase-3 inhibitor) and/or TRAIL on pro-apoptotic Bcl-2 family proteins such as Bim and Bid. Here we demonstrate that the combination of MG-132 and TRAIL induced significant apoptotic cell death in both cell lines, HF28GFP and HF28BclxL. Apoptosis correlated with a decrease of phospho-ERK1/2, the accumulation of Bim and translocation of truncated Bid (tBid) and jBid. In addition, the combination of MG-132 and TRAIL seemed to target other apoptotic factors, which led to the accumulation of active capsase-3. Furthermore, co-stimulation of LiCl and TRAIL induced apoptosis in HF28GFP cells. However, HF28Bcl-xL cells were far less sensitive to the combinatorial effects of LiCl and TRAIL. Interestingly, we observed that LiCl did not target Bim and Bid proteins. In conclusion, these data show that targeting of pro-apoptotic Bcl-2 family proteins simultaneously through a selective proteasome inhibition might help to overcome TRAIL resistance caused by overexpression of anti-apoptotic Bcl-2 family proteins. Moreover, the data may provide new strategies to develop targeted therapies against lymphomas.
Subject: TRAIL
MG-132
Bcl-2 family proteins
XIAP
Follicular lymphoma
Caspases
BCL-2 FAMILY PROTEINS
IN-VITRO MODEL
DEGRADATION CONTRIBUTES
PROTEASOME INHIBITORS
MEDIATED APOPTOSIS
PATHWAYS
PHOSPHORYLATION
EXPRESSION
SELECTION
3122 Cancers
3111 Biomedicine
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