Functional characterization of NAD dependent de-acetylases SIRT1 and SIRT2 in B-Cell Chronic Lymphocytic Leukemia (CLL)

Cancer Biology & Therapy
Savita Bhalla, Leo I Gordon

Abstract

Sirtuins (SIRT) are nicotinamide adenine dinucleotide (NAD+) dependent deacetylases or ADP- ribosyl transferases (ARTs) that deacetylate lysine residues on various proteins regulating a variety of cellular and metabolic processes. These enzymes regulate metabolism, cell survival, differentiation and DNA repair. SIRT proteins play an important role in the survival and drug resistance of cancer cells. The purpose of the present study was to investigate the expression and role of SIRT in chronic lymphocytic leukemia (CLL). We analyzed the expression of SIRT1 and SIRT2 in CLL and normal B cells using the Oncomine database as well as by Western blotting of fresh CLL cells from patients and pro-lymphocytic leukemia (PLL) cell lines, JVM-3 and MEC-2. We showed that both primary CLL cells and JVM-3 and MEC-2 cell lines overexpress high levels of functional SIRT1 and SIRT2. SIRT inhibitors EX-527 and sirtinol impair cell growth, induce ROS production, loss of mitochondrial membrane potential and apoptosis in primary CLL cells and cell lines. Using shRNA knock down of SIRT1 and SIRT2 in JVM-3 and MEC-2 cell lines, we showed that expression of both proteins is crucial for the survival of these cells. Furthermore, studies in nutrient depri...Continue Reading

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Citations

May 16, 2019·Journal of Zhejiang University. Science. B·Fei-Teng HuangLing Li
Jan 19, 2019·Oncology Letters·Shajedul IslamItsuo Chiba
Feb 2, 2019·World Journal of Experimental Medicine·Bruno GhirottoPaulo José Basso
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Sep 11, 2019·Ageing Research Reviews·Yan WangLili Cui
Jan 14, 2021·International Journal of Molecular Sciences·Ewa Maria KratzAgnieszka Piwowar
Nov 22, 2020·European Journal of Pharmacology·María Paula CeballosMaría Cristina Carrillo
Jun 21, 2021·Biochimica Et Biophysica Acta. General Subjects·Liz M Garcia-Peterson, Xiaoling Li

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Methods Mentioned

BETA
flow cytometry
flow
FCS
acetylation
FACS
transfection
protein assay

Software Mentioned

Image
Oncomine
FCS express

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