Journal: Molecular Medicine Reports

Article Title: Advances regarding physiological functions and mechanisms of theaflavin-3,3'-digallate (Review)

doi: 10.3892/mmr.2026.13837

Figure Lengend Snippet: Schematic illustration of the molecular mechanisms of TF3 in antioxidant defense, inflammation suppression and tumor inhibition. (A) Antioxidant mechanism of TF3. In normal cells, TF3 markedly decreases ROS levels by promoting the dissociation of Nrf2 from Keap1 inducing Nrf2 phosphorylation, and facilitating its translocation into the nucleus to interact with ARE, which initiates transcription of HO-1, SODs, GPx and CATs. In cancer cells, TF3 decreases GSH levels, disrupts redox homeostasis and activates caspase-3, resulting in increased PARP cleavage (cleaved PARP ↑) and apoptosis. By contrast, in normal cells, TF3 maintains redox balance and reduces PARP cleavage (cleaved PARP ↓). (B) Anti-inflammatory mechanism of TF3. TF3 reduces the levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 by suppressing the activation of MAPK, JNK and NF-κB. (C) Antitumor mechanism of TF3. TF3 decreases GSH levels to reduce efflux relaxation of cisplatin and improve the expression of copper CTR1, which heightens the sensitivity of ovarian cancer cells to cisplatin. When EGF activates HER2, SHC1 dissociates from SHCBP1 and is recruited by HER2 to activate the classical MAPK and PI3K signaling pathways. Dissociated SHCBP1 enters the nucleus and interacts with PLK1, which promotes phosphorylation of the mitotic protein MISP to regulate mitosis. TF3 attenuates tumor cell-induced angiogenesis by suppressing the cleavage of Notch-1 and subsequently decreasing HIF-1α, c-Myc and VEGF expression. TF3, theaflavin-3,3′-digallate; ROS, reactive oxygen species; GSH, glutathione; ARE, antioxidant response element; HO-1, heme oxygenase-1; SODs, superoxide dismutases; GPx, GSH peroxidase; CATs, catalases; PARP, poly(ADP-ribose) polymerase; CTR1, copper transporter 1; SHC1, Src homology 2 domain-containing transforming protein 1; SHCBP1, Shc SH2-domain binding protein 1; PLK1, polo-like kinase 1; MISP, mitotic spindle positioning protein; HIF-1α, hypoxia-inducible factor 1α; TNBS, 2,4,6-trinitrobenzenesulfonic acid; MKK, mitogen-activated protein kinase kinase; Keap1, Kelch-like ECH-associated protein 1; Nrf2, nuclear factor erythroid 2-related factor 2; LPS, lipopolysaccharide; TNFSF14, TNF superfamily member 14; ATP7A/7B, ATPase copper transporting α/β; FasL, Fas ligand; MRP2, resistance-associated protein 2; P, phosphorylated.

Article Snippet: Yoshino et al , 2010 , In vitro / in vivo , Mouse type IV allergic model; determination of antioxidant activities , Supplied by Unilever Japan KK , Antioxidant activity ↑, and IL-12, IFN-γ and TNF-α ↓ , ( ) .

Techniques: Inhibition, Phospho-proteomics, Translocation Assay, Activation Assay, Expressing, Protein-Protein interactions, Binding Assay