ArticleMolecules (Basel, Switzerland)2026
Changes in HDAC Expression and Activity by Oolongtheanin Digallate and Theasinensins and the Onset of Apoptosis.
Article in Molecules (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Epigallocatechin gallate (EGCG) is the major polyphenol in green tea and is frequently used in food supplements. In recent years, numerous studies have highlighted the bioactivity of polyphenols beyond their established role as radical scavengers. However, EGCG is highly unstable in slightly basic solutions such as cell culture medium. It therefore remains unclear whether the biological effects attributed to EGCG are caused by the parent compound itself or by its oxidation products, including the dimers examined here. In this study, the effects of EGCG focusing on apoptosis induction and histone deacetylases (HDAC) were compared with those of its major oxidation products, theasinensin A (TSA), theasinensin D (TSD), and oolongtheanin digallate (OTDG), in the human hepatocellular carcinoma cell line HepG2. The induction of cellular pathways involved in apoptosis was investigated using several in vitro biochemical approaches. Transcriptional analysis of apoptosis-associated genes revealed distinct expression profiles, and caspase activities were differentially affected by the test compounds. HDAC activity in nuclear protein extracts was significantly reduced after incubation with the stabilized oxidation products, whereas no comparable HDAC-inhibitory effect was observed after direct incubation of HepG2 cells. Nevertheless, HDAC gene expression, particularly of class I isoforms, was modulated by the test compounds in the low micromolar range. These effects diminished at concentrations associated with the onset of apoptosis. Furthermore, untargeted proteomics identified ribosomal proteins as additional cellular targets. Overall, these findings help to clarify the contribution of abundant EGCG oxidation products to the antiproliferative and HDAC modulating effects commonly attributed to the parent compound under cell culture conditions, underscoring the importance of investigating these oxidation products.
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