Chini 2014 Clin Cancer Res: Difference between revisions
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{{Publication | {{Publication | ||
|title=Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN ( | |title=Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN (2014) Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy for pancreatic tumors. Clin Cancer Res 20:120-30. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24025713 PMID: 24025713] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/24025713 PMID: 24025713] | ||
|authors=Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN | |authors=Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN | ||
|year= | |year=2014 | ||
|journal=Clin Cancer Res | |journal=Clin Cancer Res | ||
|abstract= | |abstract=Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth. | ||
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. | |||
We demonstrated that pharmacological 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 by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1, nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth ''in vitro'' and ''in vivo'' and further increases the sensitivity to Nampt inhibition. | |||
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We demonstrated that pharmacological 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 by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1, nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo and further increases the sensitivity to Nampt inhibition. | |||
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Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer. | Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer. | ||
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}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, nDNA;cell genetics | |||
|diseases=Cancer | |||
|organism=Human | |||
|tissues=Islet cell;pancreas;thymus, Other cell lines | |||
|preparations=Intact cells | |||
|couplingstates=ROUTINE, ET | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 17:21, 9 November 2017
Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN (2014) Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy for pancreatic tumors. Clin Cancer Res 20:120-30. |
Chini CC, Gonzalez Guerrico A, Nin V, Camacho-Pereira J, Escande C, Barbosa M, Chini EN (2014) Clin Cancer Res
Abstract: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth.
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.
We demonstrated that pharmacological 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 by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1, nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo and further increases the sensitivity to Nampt inhibition.
Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer.
โข O2k-Network Lab: BR Rio de Janeiro Galina A
Labels: MiParea: Respiration, nDNA;cell genetics
Pathology: Cancer
Organism: Human Tissue;cell: Islet cell;pancreas;thymus, Other cell lines Preparation: Intact cells
Coupling state: ROUTINE, ET
HRR: Oxygraph-2k