Nicotinamide and CLL

[Guest guest]

Nicotinamide is otherwise known as niacinamide or vitamin B3. It is readily

available and very cheap.

It is a commonly used vitamin in megadose therapy as it is water soluble and

will not build up in the system.

Personally, I doubt that we have overlooked the affect on CLL from this vitamin.

I don't think niacinamide as a single agent will do anything to treat CLL.

Perhaps, in combination, it may prove to have an effect.

Nicotinamide Blocks Proliferation and Induces Apoptosis

of CLL Cells through Activation of the p53/miR-34a/SIRT1 Tumor Suppressor

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Nicotinamide Blocks Proliferation and Induces Apoptosis of Chronic Lymphocytic

Leukemia Cells through Activation of the p53/miR-34a/SIRT1 Tumor Suppressor

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670-9535; Fax: 39-011-670-9546; E-mails: silvia.deaglio@... or

fabio.malavasi@...

Abstract

Because of its relatively indolent clinical course, chronic lymphocytic leukemia

(CLL) offers a versatile model for testing novel therapeutic regimens and drug

combinations. Nicotinamide is the main NAD+ precursor and a direct inhibitor of

four classes of enzymes, including the sirtuins. SIRT1, the main member of the

sirtuin family, inactivates p53 by deacetylating a critical lysine residue.

In this study, we showed that CLL cells express high levels of functional SIRT1,

which is inhibited by exogenous nicotinamide. This agent blocks proliferation

and promotes apoptosis selectively in leukemic cells that express wild-type (wt)

p53. Nicotinamide modulates the p53-dependent genes p21, NOXA, BAX, and Mcl-1,

indicating an activation of the p53 pathway and of caspase-3. DNA-damaging

chemotherapeutics, such as etoposide, activate a functional loop linking SIRT1

and p53 through the induction of miR-34a. When leukemic cells are simultaneously

exposed to nicotinamide and etoposide, we observe a significant increase in

miR-34a levels with a concomitant inhibition of SIRT1. Furthermore, p53

acetylation levels are higher than with either agent used alone. Overall,

treatment with both nicotinamde and etoposide shows strongly synergistic effects

in the induction of apoptosis.

We therefore concluded that nicotinamide has the dual property of inhibiting

SIRT1 through a noncompetitive enzymatic block (p53 independent) and at the same

time through miR-34a induction (p53 dependent). These observations suggested the

therapeutic potential of nicotinamide, a novel, safe, and inexpensive drug, to

be used in addition to chemotherapy for CLL patients with wt p53. Cancer Res;

71(13); 4473–83. ©2011 AACR.