Epigallocatechin-3-gallate Synergistically Enhanced Arecoline-Induced Cytotoxicity by Redirecting Cycle Arrest to Apoptosis

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Abstract
Carcinogens, such as arecoline, play a crucial role in cancer progression and continuous gene mutations by generating reactive oxygen species (ROS). Antioxidants can reduce ROS levels and potentially prevent cancer progression but may paradoxically enhance the survival of cancer cells. This study investigated whether epigallocatechin-3-gallate (EGCG), an antioxidant from green tea, could resolve this paradox. Prostate cancer cells (PC-3 cell line) were cultured and treated with arecoline combined with NAC (N-acetylcysteine) or EGCG; the combined effects on intracellular ROS levels and cell viability were examined using the MTT and DCFDA assays, respectively. In addition, apoptosis, cell cycle, and protein expression were investigated using flow cytometry and western blot analysis. Our results showed that EGCG, similar to NAC (N-acetylcysteine), reduced the intracellular ROS levels, which were elevated by arecoline. Moreover, EGCG not only caused cell cycle arrest but also facilitated cell apoptosis in arecoline-treated cells in a synergistic manner. These were evidenced by elevated levels of cyclin B1 and p27, and increased fragmentation of procaspase-3, PARP, and DNA. Our findings highlight the potential use of EGCG for cancer prevention and therapy.
Funding Information
  • National Science and Technology Council, Taiwan (MOST106-2320-B-008-008-MY3, MOST109-2320-B-008-001-MY3, 11001-62-021, TPCH-110-05, TYAFGH-E-111053, TYAFGH-E-112050, MND-MAB-110-025, MND-MAB-C-11107-111026)
  • Taipei City Hospital, Department of Health, Taipei City Government, Taipei, Taiwan (MOST106-2320-B-008-008-MY3, MOST109-2320-B-008-001-MY3, 11001-62-021, TPCH-110-05, TYAFGH-E-111053, TYAFGH-E-112050, MND-MAB-110-025, MND-MAB-C-11107-111026)
  • Taoyuan Armed Forces General Hospital (MOST106-2320-B-008-008-MY3, MOST109-2320-B-008-001-MY3, 11001-62-021, TPCH-110-05, TYAFGH-E-111053, TYAFGH-E-112050, MND-MAB-110-025, MND-MAB-C-11107-111026)
  • National Defense Medical Center (MOST106-2320-B-008-008-MY3, MOST109-2320-B-008-001-MY3, 11001-62-021, TPCH-110-05, TYAFGH-E-111053, TYAFGH-E-112050, MND-MAB-110-025, MND-MAB-C-11107-111026)

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