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TY - JOUR JO - Advances in Clinical and Experimental Medicine J2 - Adv Clin Exp Med SN - 1899-5276 PB - Wroclaw Medical University VL - 33 IS - 11 PY - 2024 ID - Han2024-11-29 TI - Parthenolide induces ROS-dependent cell death in human gastric cancer cell AB - Background. Parthenolide (PN), a key active ingredient of feverfew, has been used to treat gastrointestinal disorders. However, the mechanism of the cytotoxic effect exerted by PN on tumor cells has not been elucidated.Objectives. To study the cytotoxic effect of PN on human gastric cancer cells, the specific death mode, and gene expression changes induced by PN.Material and Methods. In this study, MGC-803 cells were used to study PN-induced cytotoxicity as a gastric cancer cell line. Assays of cell proliferation, cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometer. MGC-803 cells treated with and without PN were separately subjected to high-throughput RNA sequencing. Western blotting was used to investigate the expression of some important proteins.Results. Parthenolide exposure elicited cell proliferation inhibition in a doseand time-dependent manner. Parthenolide induced cell cycle arrest at the G1 and S stages. Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL. MGC-803 cells showed a response to ROS and oxidative stress after PN treatment. Moreover, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase.Conclusion. Parthenolide-induced gastric cancer cell death is a complex ROS-dependent process different from ordinary apoptosis and necrosis, suggesting that PN is a potential treatment option for gastric cancer. AU - Han, Dandan AU - Zhu, Wenhao AU - Chen, Yang AU - Wang, Huiru SP - 1237 EP - 1245 DA - 2024-11-29 DO - 10.17219/acem/175152 UR - http://dx.doi.org/10.17219/acem/175152 ER -