PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53

PRIMA-1Met has shown promising preclinical activity in various cancer types. However, its effect on Waldenström's Macroglobulinemia (WM) cells as well as its exact mechanism of action is still elusive. In this study, we evaluated the anti- tumor activity of PRIMA-1Met alone and in combination w...

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Bibliographic Details
Published in:Cancer biology & therapy 2015-01, Vol.16 (5), p.799-806
Main Authors: Sobhani, Mona, Abdi, Jahangir, Manujendra, Saha N, Chen, Christine, Chang, Hong
Format: Article
Language:English
Subjects:
Apoptosis
Cell Line, Tumor
dexamethasone or bortezomib
Humans
PRIMA-1Met
Quinuclidines - metabolism
Research Paper
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Waldenstrom Macroglobulinemia - drug therapy
Waldenström's Macroglobulinemia
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Summary:PRIMA-1Met has shown promising preclinical activity in various cancer types. However, its effect on Waldenström's Macroglobulinemia (WM) cells as well as its exact mechanism of action is still elusive. In this study, we evaluated the anti- tumor activity of PRIMA-1Met alone and in combination with dexamethasone or bortezomib in WM cell lines and primary samples. Treatment of WM cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of migration and suppression of colony formation. Upon PRIMA-1Met treatment, p73 was upregulated and Bcl-xL was down-regulated while no significant change in expression of p53 was observed. Furthermore, siRNA knockdown of p53 in WM cell line did not influence the PRIMA-1Met-induced apoptotic response whereas silencing of p73 inhibited latter response in WM cells. Importantly, combined treatment of BCWM-1 cells with PRIMA-1Met and dexamethasone or bortezomib induced synergistic reduction in cell survival. Our study provides insights into the mechanisms of anti-WM activity of PRIMA-1Met and supports further clinical evaluation of PRIMA-1Met as a potential novel therapeutic intervention in WM.
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2015.1026482