Anticancer agent CHS-828 inhibits cellular synthesis of NAD
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Anticancer agent CHS-828 inhibits cellular synthesis of NAD. / Olesen, U.H.; Christensen, M.K.; Bjorkling, F.; Jaattela, M.; Jensen, P.B.; Sehested, M.; Nielsen, S.J.
I: Biochemical and Biophysical Research Communications, Bind 367, Nr. 4, 2008, s. 799-804.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Anticancer agent CHS-828 inhibits cellular synthesis of NAD
AU - Olesen, U.H.
AU - Christensen, M.K.
AU - Bjorkling, F.
AU - Jaattela, M.
AU - Jensen, P.B.
AU - Sehested, M.
AU - Nielsen, S.J.
PY - 2008
Y1 - 2008
N2 - Malignant cells display increased demands for energy production and DNA repair. Nicotinamide adenine dinucleotide (NAD) is required for both processes and is also continuously degraded by cellular enzymes. Nicotinamide phosphoribosyltransferase (Nampt) is a crucial factor in the resynthesis of NAD, and thus in cancer cell survival. Here, we establish the cytotoxic mechanism of action of the small molecule inhibitor CHS-828 to result from impaired synthesis of NAD. Initially, we detected cross-resistance in cells between CHS-828 and a known inhibitor of Nampt, FK866, a compound of a structurally different class. We then showed that nicotinamide protects against CHS-828-mediated cytotoxicity. Finally, we observed that treatment with CHS-828 depletes cellular NAD levels in sensitive cancer cells. In conclusion, these results strongly suggest that, like FK866, CHS-828 kills cancer cells by depleting NAD Udgivelsesdato: 2008/3/21
AB - Malignant cells display increased demands for energy production and DNA repair. Nicotinamide adenine dinucleotide (NAD) is required for both processes and is also continuously degraded by cellular enzymes. Nicotinamide phosphoribosyltransferase (Nampt) is a crucial factor in the resynthesis of NAD, and thus in cancer cell survival. Here, we establish the cytotoxic mechanism of action of the small molecule inhibitor CHS-828 to result from impaired synthesis of NAD. Initially, we detected cross-resistance in cells between CHS-828 and a known inhibitor of Nampt, FK866, a compound of a structurally different class. We then showed that nicotinamide protects against CHS-828-mediated cytotoxicity. Finally, we observed that treatment with CHS-828 depletes cellular NAD levels in sensitive cancer cells. In conclusion, these results strongly suggest that, like FK866, CHS-828 kills cancer cells by depleting NAD Udgivelsesdato: 2008/3/21
M3 - Journal article
VL - 367
SP - 799
EP - 804
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
ID: 10156143