Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

Abstract

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 1,2-13 C 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. ' 2009 UICC

Tumor cell metabolism

“…92 Some studies have reported that the non-oxidative arm of PPP is the principal pathway for R5P synthesis in tumor cells 25,62,92. after finding a significant overexpression of the transketolase-like 1 (TKTL1) enzyme in progressing tumors. 96 However, other reports have indicated that both G6PDH and TKTL1 are overexpressed during the cell cycle progression of a human colon cancer cell line 97 and in (pre)neoplastic lesions in rat liver. 98 It is likely that cancer cells acquire diverse energy supplies that are differentially regulated during the development of the disease.…”

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

“…In agreement with the present study, Frederiks et al (2007) reported a massive ultrastructural localization of G-6-PD in the cytoplasm of colon carcinoma cells, whereas human colon cancer cells contained five times higher G-6-PD activity than hepatoma cells. Vizán et al (2009) found that G-6-PD, the key enzyme of the oxidative branch of the pentose phosphate pathway (which is necessary for nucleotide synthesis), is enhanced during cell cycle progression of the human colon cancer cell line. This enhanced enzyme activity coincides with an increased ratio of the pentose monophosphate to the hexose monophosphate pool during late G1 and S phases of cell cycle, suggesting a potential role for pentose phosphates in proliferation signalling.…”

“…Some investigations have dealt with pyruvate kinase (PK) activity among different grades of malignancy in colorectal cancer (Shin et al 2009). Glucose-6-phosphate dehydrogenase (G-6-PD) has also been reported in a human adenocarcinoma cancer cell line (Vizán et al 2009). …”

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets

“…This observation reflects the well-known fact that immunoblotting techniques are more sensitive detection methods than mass spectrometry, particularly for low abundance proteins. G6PD is the key regulatory enzyme in PPP and necessary for the synthesis of nucleotides and nucleic acids (39)(40)(41). Recent studies have demonstrated that G6PD activity is suppressed in cells containing wild-type p53 through a direct inhibition; whereas, it is not subjected to such negative regulation in cells containing mutant p53 (42).…”