# Consequences of Glucose Enriched Diet on Oncologic Patients
### Role of Sugar in Cancer Metabolism
#### 1.2.1 Sugars in the Diet and Cancer Risk
This family of proteins is divided into antiapoptotic multidomain proteins (prototypes: Bcl-XL and Bcl-2), which contain four BH domains (BH1234), which correspond to the \(\alpha\)-helix segment (Figure 2) [33; 34]; multidomain proteins (prototypes: Bak and Bax), containing three BH domains (BH 123); and pro-apoptotic proteins BH3 (prototypes: Bad and Bid) [35]. The principal location of action of Bcl-2-like proteins is presumably the mitochondrial membrane [36]. Figure 2: Representation of the action of glucose in cells. Glucose deprivation results in AMPK-dependent mTor inactivation. Furthermore, the activation of AMPK leads to p53 activation and upregulation of the BH3-only proteins. The BH3-only proteins are induced by AMPK activation as well as by the ER stress response, and they participate in apoptosis on glucose deprivation, probably by inhibiting Mcl-1. In most situations, a sequence conservation is present in all four domains of the anti-apoptotic components. Pro-apoptotic molecules usually show poorer sequence conservation of the first \(\alpha\)-helical region, BH4 [37]. Originally integral membrane proteins, anti-apoptotic components can be situated in the endoplasmic reticulum, mitochondria, or nuclear membrane [38; 39; 40]. On the contrary, a large part of certain pro-apoptotic components are located in the cytosol or the cytoskeleton prior to the death signal [41]. Under certain circumstances, pro-apoptotic stimuli stimulate a signaling of the (AP) -1/p53 transduction pathway; these families of transcription factors control the Bax promoter, leading to apoptosis dependent on protein synthesis by increasing the Bax/Bcl-2 ratio and Bax levels [42]. Nevertheless, apoptotic stimuli often activate more than Bax regulation. Chaperones in the cytoplasm of live cells contain the protein Bax such as Ku/70 [43] and 14-3-3 [44]. Apoptotic stimuli release Bax through Ku70 acetylation [45] or JNK-dependent 14-3-3 phosphorylation [46]. Bax release is essential but not enough for triggering, and there must be further particular events. Bax can be triggered by a number of stimuli, through unique processes that are focused on different domains of the protein, and can lead to diverse end consequences [47]. The mPTP is a megachannel that forms in the mitochondrial membrane at the location where the outer and inner mitochondrial membranes meet, and it is considered a vital step for the intrinsic pathway of apoptosis [36; 48]. Several members of the Bcl-2 protein family are recruited to assist pore formation in its high conductance state under circumstances such as calcium excess, low ATP levels, and oxidative stress [7; 36; 48; 49; 50]. Several members of the Bcl-2 family are activated during apoptosis. Caspase 8 activation, for example, triggers rapid stimulation of Bid as well as its translocation to mitochondria as Bid via stimulation of Fas in the plasma membrane. With a molecular weight of 15 kDa, tBid can bind to Bax, allowing it to cling to the mitochondrial membrane, which is needed for the release of cytochrome c and the activation of MAP-1 [51; 52; 53]. Antiglycolytic medicines and glucose deprivation trigger tumor cell death, which can occur through caspase-8-mediated or mitochondrial apoptosis or necrosis. In the case of caspase-8, it is known that it activates the effector caspases [54; 55], principally by the cleavage of the Bcl-2 family member Bid and the consequent activation of the mitochondrial pathway, which serves as an amplifier of the signal [55; 56; 57]. Antiapoptotic proteins of the Bcl-2 family prevent tumor cells from dying as a result of glucose restriction, which may indicate that glucose deprivation leads to mitochondrial apoptosis. For example, a research on the MCF-7 line of multidrug-resistant breast cancer demonstrated that, in the event of glucose deprivation, these cells suffer apoptosis, which may be avoided by the overexpression of Bcl-2.