Probing into the chemopreventive properties of synthetic 1,3,6-tri-O-galloyl-α-D-glucose (α-TGG) against glioblastoma and triple-negative breast cancer-derived cell models

Abstract

Inflammation plays a significant role in cancer progression. Chemopreventive strategies against cellular response to pro-inflammatory cues may therefore contribute to inhibit the acquisition of an invasive phenotype. 1,3,6-Tri-O-Galloyl-β-D-Glucose (β-TGG) is a type of gallotannin naturally found in plants like Paeonia lactiflora and Terminalia chebula. Unfortunately, the overall yields of β-TGG extraction require complex purification protocols from plant sources and are relatively low. Here, a new synthetic α-anomer of TGG (α-TGG) was characterized for anti-inflammatory and anticancer biological properties. In vitro pro-inflammatory and epithelial-to-mesenchymal transition (EMT) cues, triggered by phorbol 12-myristate 13-acetate (PMA), concanavalin A (ConA), tumor necrosis factor (TNF) α, and transforming growth factor (TGF) β, were used to screen α-TGG in two highly aggressive human cancer cell models, namely the U87 glioblastoma and the MDA-MB-231 triple-negative breast cancer (TNBC)-derived cells. α-TGG dose-dependently inhibited ConA-mediated activation of the latent matrix metalloproteinase pro-MMP-2 into its active MMP-2 form as well as the ConA- and PMA-mediated cyclooxygenase (COX)-2 expression, two biomarkers of inflammation, in U87 cells. In MDA-MB-231, α-TGG inhibited PMA- and TNFα-mediated induction of pro-MMP-9, a marker of inflammation and invasive phenotype. Finally, in both cell lines, α-TGG further inhibited TGFβ-induced chemotaxis, as well as TGFβ-induced Smad2 phosphorylation and Snail expression, crucial upstream signaling pathway and downstream biomarkers associated with EMT. Collectively, we confirm that α-TGG retained potent anti-inflammatory and anti-invasive pharmacological properties which support its chemopreventive potential.