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Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy for pancreatic tumors.


ABSTRACT:

Purpose

Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth.

Experimental design

We used human pancreatic cancer cells, both in vitro (cell culture experiments) and in vivo (xenograft experiments), to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth.

Results

We demonstrated that pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. These changes were accompanied by a reduction of NAD levels, glycolytic flux, lactate production, mitochondrial function, and levels of ATP. The massive reduction in overall metabolic activity induced by Nampt inhibition was accompanied b

SUBMITTER: Chini CC 

PROVIDER: S-EPMC3947324 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature