Abstract
Abstract
Background: Theaflavin-1 (TF1), a major polyphenolic component of black tea, has shown anticancer activity in several tumor models. However, its effects and molecular mechanisms in gastric cancer remain insufficiently characterized.
Methods: For this purpose,Cell viability was evaluated in SGC-7901, MGC-803, and GES-1 cells using CCK-8 and colony formation assays. Hoechst 33258 staining was used to observe apoptotic nuclear morphology, flow cytometry was used to quantify apoptosis, and the wound-healing assay was used to assess cell migration. Transcriptome sequencing, qRT-PCR, mitochondrial membrane potential analysis, reactive oxygen species (ROS) detection, and western blotting were performed to investigate the underlying mechanisms.
Results: TF1 significantly inhibited the viability, clonogenicity, and migration of SGC-7901 and MGC-803 cells in a dose-dependent manner, while exerting minimal toxicity toward normal GES-1 cells. TF1 also induced apoptosis and mitochondrial membrane depolarization. Transcriptome sequencing identified the p53 signaling pathway as a major pathway altered by TF1 treatment. Western blotting showed that TF1 increased the expression of Bax, p53, p21, cytochrome c, and cleaved caspase-3, whereas it decreased the expression of Bcl-2, CDK6, PCNA, N-cadherin, and Vimentin. TF1 also elevated intracellular ROS levels, and pretreatment with N-acetylcysteine partially reversed these changes.
Conclusion: TF1 suppresses gastric cancer cell growth and migration and promotes apoptosis through a ROS-p53-mitochondrial signaling axis. These findings support TF1 as a promising natural candidate for further investigation in gastric cancer therapy.