TY - JOUR
T1 - Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29
AU - Vizán, Pedro
AU - Alcarraz-Vizán, Gema
AU - Díaz-Moralli, Santiago
AU - Solovjeva, Olga N.
AU - Frederiks, Wilma M.
AU - Cascante, Marta
PY - 2009/6/15
Y1 - 2009/6/15
N2 - Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2-13C 2-glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments.
AB - Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2-13C 2-glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments.
KW - Cell cycle progression
KW - Glucose-6-phosphate dehydrogenase
KW - Metabolic checkpoint
KW - Metabolic isotopomer distribution analysis (MIDA)
KW - Pentose phosphate pathway
KW - Pentose phosphates
KW - Transketolase
UR - http://www.scopus.com/inward/record.url?scp=65649120706&partnerID=8YFLogxK
U2 - 10.1002/ijc.24262
DO - 10.1002/ijc.24262
M3 - Article
C2 - 19253370
AN - SCOPUS:65649120706
SN - 0020-7136
VL - 124
SP - 2789
EP - 2796
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -