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Mei Yang, Weihua Zhang, Xiuxiu Yu, Feng Wang, Yeping Li, Yan Zhang, Yu Yang
(Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland))
Med Sci Monit 2021; 27:e930083
Helenalin is a pseudoguaianolide natural product with anti-cancer activities. This study investigated the underlying mechanism of the anti-prostate cancer effects of helenalin in vitro.
MATERIAL AND METHODS: CCK-8 assay was performed to detect the optimal concentrations of helenalin in DU145 and PC-3 cells. After exposure to helenalin and/or reactive oxygen species (ROS) inhibitor, ROS production was assessed by DCFH-DA staining. Thioredoxin reductase-1 (TrxR1) expression was detected by RT-qPCR and western blot. Moreover, apoptosis and cell cycle were evaluated by flow cytometry. Following TrxR1 knockdown or overexpression, TrxR1 expression, ROS generation, apoptosis, cell cycle, migration, and invasion were examined in cells co-treated with helenalin.
RESULTS: Helenalin distinctly repressed the viability of prostate cancer cells in a concentration-dependent manner. We chose 8 μM and 4 μM as the optimal concentrations of helenalin for DU145 and PC-3 cells, respectively. Helenalin treatment markedly triggered ROS production and lowered TrxR1 expression, which was ameliorated by ROS inhibitor. Exposure to helenalin facilitated apoptosis as well as G0/G1 cell cycle arrest, which was reversed by ROS inhibitor. Helenalin relieved the inhibitory effect of TrxR1 on ROS production. Furthermore, helenalin ameliorated the decrease in apoptosis rate and the shortening of G0/G1 phase as well as the increase in migration and invasion induced by TrxR1 overexpression.
CONCLUSIONS: Our findings revealed that helenalin accelerated ROS-mediated apoptosis and cell cycle arrest via targeting TrxR1 in human prostate cancer cells.
Keywords: Apoptosis, Cell Cycle, Prostatic Neoplasms, Reactive Oxygen Species, thioredoxins