Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as antagonists of the glucose transporter GLUT1

Abstract

We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by deprivation of the glucose uptake through blocking of GLUT1 and by formation of sequestering nanonet through biocatalytic self-assembly.

Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse

“…Glycolysis deprivation via blockage of GLUT1 by 1 and 2 was also studied as an additional contributor to cell death. 12 As noted, spheroids have a higher expression of GLUT1 as compared to the 2D cell culture (Figure 1c). We knocked down GLUT1 expression in the spheroids by transfection with three target-specific siRNAs (Figure S6).…”

“…The phosphorylated precursor 1 and its dephosphorylated analogue 2 contain a glucose moiety that interacts with glucose transporter 1 (GLUT1) (Scheme 1d), overexpressed in different cancers, thus, allowing double targeting, as we recently demonstrated. 12 We have selected three cell lines for spheroid formation, namely SaOs2 osteosarcoma, HS578T breast and MCF7 breast cancer cells because they all overexpress ALP, GLUT1 and caveolin 1 (CAV1) (Figure S1). 13 Our interests in GLUT1-and ALPoverexpressing cell lines is related to the affinity of compound 1 for those proteins: 1 can bind to GLUT1 because of the glucose moiety (Scheme 1d) and can be transformed in the selfassembling 2 upon ALP action (Scheme 1c).…”

“…13 Our interests in GLUT1-and ALPoverexpressing cell lines is related to the affinity of compound 1 for those proteins: 1 can bind to GLUT1 because of the glucose moiety (Scheme 1d) and can be transformed in the selfassembling 2 upon ALP action (Scheme 1c). 4,12 In addition to GLUT1 and ALP, we also explored the contribution of CAV1 in carbohydrate amphiphile mediated BSA processes. CAV1 is the main structural protein of caveolae, the small pockets in the cell membrane that are known to modulate the glycolysis and to interact dynamically with ALP.…”

Dynamic supramolecular self-assembly of platinum(ii) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death

“…Such molecular amphiphiles, as exemplied by the amphiphilic peptides or aromatic carbohydrates that assemble into brous superstructures upon biological triggers (e.g., pH variation or enzymatic action), impair the organelle-specic functions and hence impede the cancer cell proliferation. 23,39,40 In the literature, nanostructures/particles made of iron oxide, gold, quantum dots or titanium dioxide have been exploited as potential therapeutics in modulating the autophagic process by impairing the functional pH gradient and membrane permeability of lysosomes through an endocytosismediated uptake mechanism. 41 In this work, we demonstrated the use of supramolecular self-assembly of a platinum(II) complex, as exemplied by a glucose-appended platinum(II) terpyridyl arylacetylide, as an anti-cancer strategy to perturb the autophagy-lysosomal system and trigger cancer cell death (Fig.…”

Click Pt(IV)-Carbohydrates Pro-Drugs for Treatment of Osteosarcoma

“…In addition, we investigated the effect of the linker connecting these structural moieties by the formation of anomeric N -triazolyl or O -ethylene glycosides ( Figure 1B ). Anomeric triazoles can offer additional sites of interaction for glucose transporters and hence enhance the activity of these types of derivatives compared to conventional glycosides ( Brito et al, 2020 ; Ottoni et al, 2020 ). The anticancer activity and the cellular uptake of the complexes have been tested against three different osteosarcoma cell lines and in a model of enriched-cancer stem cells, in order to compare in vitro the effectiveness with standard cisplatin.…”