# Consequences of Glucose Enriched Diet on Oncologic Patients
### Role of Sugar in Cancer Metabolism
#### 1.2.1 Sugars in the Diet and Cancer Risk
Furthermore, in Ba/F3 hematopoietic cells, it has been proven that under low glucose circumstances, constant synthesis of the antiapoptotic homolog Bcl-2 Bcl-xL inhibits cells from apoptosis as a result of IL-3 deficiency [26]. It has also been shown that Mcl-1, another member of the anti-apoptotic Bcl-2 family, plays a role in glucose deprivation-induced apoptosis, since reducing Mcl-1 levels sensitized the acute leukemia cell line Jurkat T-cell to glucose removal. It has been demonstrated that, by limiting its breakdown, the employment of glycolysis in hematopoietic cells maintains the equilibrium of Mcl-1 [58]. In contrast, as noted above, glucose deprivation resulted in AMPK-dependent deactivation of mTor; this was seen when the translation of Mcl-1 was suppressed. Therefore, Mcl-1 is regulated at translational and post-translational levels by glycolytic metabolism. Cells are made more vulnerable to pro-apoptotic stimuli by glucose restriction, and it is believed that Mcl-1 down-regulation has a primary role in this sensitivity [26]. Glucose Controls BH3-Only Proteins  
The so-called BH3-only proteins control apoptosis by triggering Bax/Bak activation, either directly or indirectly, by blocking anti-apoptotic proteins Bcl-2 and sensing signalsarising from diverse cellular processes [27]. BH3-only proteins have major roles in the sensitivity to chemotherapy and cancer. Some of these proteins have a key function to play in glucose deprivation-induced apoptosis in diverse settings [26]. Bim has been related to the production of cell death in numerous kinds of cells and tissues in response to several stimuli. It is the major BH3-only protein connected to stress-induced cell death. It was demonstrated that Bim as well as PUMA are activated in hematopoietic cells exposed to glucose deprivation, suggesting that the stimulation of Bim under glucose deprivation could be driven by the stimulation of ER stress. In contrast, in hematopoietic cells, the administration of glycolysis produced prevention of apoptosis triggered by Bim and overexpression of Mcl-1 [26]. Glucose restriction enhances AMPK-dependent mTor deactivation with consequent suppression of Mcl-1 translation. Induction of AMPK leads to the stimulation of p53 and the overexpression of PUMA BH3-only protein. Bim is created by both the ER stress response and AMPK stimulation thanks to the transcription factor CHOP. Furthermore, Noxa participates in glucose withdrawal apoptosis in leukemic cell lines and in activated T cells, probably by decreasing Mcl-1. Eventually, Bad is post-translationally controlled in glucose shortage by blocking its phosphorylation. Thus, unphosphorylated Bad can interact with members of the Bcl-2 family and trigger apoptosis. In contrast, Bad furthermore interacts with a glucose hexokinase (HK), and the phosphorylation of Bad is important for the hexokinase's kinase activity [26]. Another BH3-only protein regulated by p53 is Noxa. Noxa has been found to contribute to glucose deprivation-induced cell death in both primary and tumor cells. Noxa was found to participate in apoptosis after glucose removal, since Noxa's down-regulation offers a competitive survival advantage to leukemic cell lines and primary T cells under low glucose conditions. It has been proposed that the involvement of Noxa in this milieu is connected with its ability to counteract the anti-apoptotic Bcl-2 homolog, Mcl-1. These data show that Noxa, similar to Bad, may have a role in both glucose deprivation-induced mortality and glucose metabolism [26]. The BH3 protein with the strongest link to glucose metabolism is named Bad. Glucose-deprived murine defective hepatocytes are protected against cell death relative to their normal counterparts. These data imply that, in response to glucose restriction, Bad operates as a proapoptotic protein distinct in the BH3 subgroup. Nevertheless, in this situation, Bad may indirectly cause cell death by regulating glucose metabolism [26].