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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Chronic Lymphocytic Leukemia | Primary research

LMW-PTP targeting potentiates the effects of drugs used in chronic lymphocytic leukemia therapy

Authors: Nagaja Capitani, Giulia Lori, Paolo Paoli, Laura Patrussi, Arianna Troilo, Cosima T. Baldari, Giovanni Raugei, Mario Milco D’Elios

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Low molecular weight protein tyrosine phosphatase (LMW-PTP) is overexpressed in different cancer types and its expression is related to more aggressive disease, reduced survival rate and drug resistance. Morin is a natural polyphenol which negatively modulates, among others, the activity of LMW-PTP, leading to the potentiation of the effects of different antitumoral drugs, representing a potential beneficial treatment against cancer.

Methods

LMW-PTP levels were measured by immunoblot analysis both in CLL cells from patients and in chronic lymphocytic leukemia (CLL)-derived Mec-1 cells. Cell viability was assessed in Mec-1 cells treated with morin alone or in combination with either fludarabine or ibrutinib or following siRNA-mediated LMW-PTP knockdown. Furthermore, the expression levels of VLA-4 and CXCR4 were assessed by both qRT-PCR and flow cytometry and both adhesion to fibronectin-coated plates and migration toward CXCL12 were analyzed in Mec-1 cells treated with morin alone or in combination with fludarabine or ibrutinib.

Results

We observed that LMW-PTP is highly expressed in Mec-1 cells as well as in leukemic B lymphocytes purified from CLL patients compared to normal B lymphocytes. Morin treatment strongly decreased LMW-PTP expression levels in Mec-1 cells and potentiated the anticancer properties of both fludarabine and ibrutinib by increasing their apoptotic effects on leukemic cells. Moreover, morin negatively regulates adhesion and CXCL12-dependent migration of Mec-1 cells by affecting VLA-4 integrin expression and CXCR4 receptor recycling.

Conclusions

Morin treatment in CLL-derived Mec-1 cell line synergizes with conventional anticancer drugs currently used in CLL therapy by affecting leukemic cell viability and trafficking.
Appendix
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Metadata
Title
LMW-PTP targeting potentiates the effects of drugs used in chronic lymphocytic leukemia therapy
Authors
Nagaja Capitani
Giulia Lori
Paolo Paoli
Laura Patrussi
Arianna Troilo
Cosima T. Baldari
Giovanni Raugei
Mario Milco D’Elios
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0786-1

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