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

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.

Citation

Mayra Montecillo-Aguado, Mario Morales-Martínez, Sara Huerta-Yepez, Mario I Vega. KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent. Leukemia & lymphoma. 2021 Jun;62(6):1422-1431

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PMID: 33410342

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