KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent

Abstract

Krüppel-like factor 4 (KLF4) is a member of the KLF transcription factor family containing zinc-fingers, and is involved in the regulation of apoptosis, proliferation and differentiation of B cells and B-cell malignancies. KLF4 can act like an oncogene, we shown that KLF4 overexpression correlated with poor prognostic and chemoresistance in B-NHL. In addition, we shown that KLF4 is regulated by YY1. In this study, we demonstrate that chemical inhibition of KLF4 by Kenpaullone, results in suppression of proliferation, cell survival, downregulation of Bcl-2 and increases apoptosis in B-NHL cell lines through YY1 independent pathway. Combination of Kenpaullone and Doxorubicin, increased apoptosis. The co-expressions of KLF4/YY1 or KLF4/Bcl-2 in NHL was analyzed using Oncomine Database, exhibiting a positive correlation of expression. The present findings suggest that the chemical inhibition of KLF4 by Kenpaullone treatment could be a potential therapeutic alternatively in KLF4⁺ lymphomas.

Keywords:

• Kenpaullone
• KLF4
• YY1
• hematological malignances
• non-Hodgkin lymphoma

Disclosure statement

Mayra Montecillo-Aguado and Mario Morales-Martínez are a doctoral students from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM). The authors declare that they have no competing interests.

Data availability statement

All data generated or analyzed during this study are included in this article.

Geolocation information

This work was carried out in Mexico with close collaboration with the USA.

Additional information

Funding

This study was supported in part by grant FIS/IMSS/PROT/G15/1417 from the IMSS (MIV). Mayra Montecillo-Aguado has received CONACyT fellowship (M. M. A. 425888/592671). M. M-M has received CONACyT fellowship (M. M-M. 739423/596754).