Dehydrocostus lactone induces autophagy, apoptosis, and oxidative stress in gastric cancer cells
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1.Basic Medical Experimental Center of Henan Medical College, Xinzheng 451191, China. 2. Department of Oncology, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450008. 3. Training Center of Nursing Department of Henan Medical College, Xinzheng 451191. 4. Department of Human Anatomy, Henan Medical College, Xinzheng 451191

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R-33

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    Abstract:

    Objective To explore the effects of dehydrocostus lactone (DHCL) on autophagy, apoptosis, and oxidative stress of gastric cancer cell line SGC-7901. Methods SGC-7901 cells cultured in vitro were divided into 0, 10, 20, and 40 μmol / L DHCL groups. Cell proliferation was analyzed by CCK-8 assays. Autophagic activity was assessed by immunofluorescence. Apoptosis was detected by flow cytometry. The levels of superoxide dismutase ( SOD ), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in culture supernatants were detected by ELISA. The level of intracellular reactive oxygen species (ROS) was detected by the DCFH-DA probe. Expression of LC3-I, LC3-II, Beclin-1, autophagy-associated protein 7 (ATG7), p62, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), BH3 interaction domain death agonist ( Bid), truncated Bid, Caspase-8, Caspase-9, Caspase-3, cleaved Caspase-8, cleaved Caspase-9, and cleaved Caspase-3 were detected by Western blot. A 0. 2 mL suspension of SGC-7901 cells (1× 107 / mL) was implanted subcutaneously. After intraperitoneal injection of 20 mg / (kg·d) DHCL for 2 weeks, tumor tissues were weighed. Results Cell survival rates in 40 and 20 μmol / L DHCL groups were lower than that in the 0 μmol / L DHCL group (P<0.05). In comparison with the 0 μmol / L DHCL group, autophagy and the apoptosis rate were higher in the 40 μmol / L and 20 μmol / L DHCL group (P<0.05). SOD and GSH-Px levels were lower than in the 0 μmol / L DHCL group (P<0.05). MDA and ROS levels were higher than in the 0 μmol / L DHCL group (P<0.05). Expression of p62 protein was lower in the 0 μmol / L DHCL group. Expression of Beclin-1, LC3II/ LC3I, ATG7, Bax / Bcl-2, tBid / Bid, cleaved Caspase-8/ Caspase-8, cleaved Caspase-9/ Caspase-9, and cleaved Caspase-3/ Caspase-3 was higher in the 0 μmol / L DHCL group (P<0.05). The nude mouse tumorigenicity assay showed that the weight of transplanted tumors in the DHCL group was lower than that in the control group (P<0.05). Conclusions DHCL promotes production of ROS in SGC-7901 cells and induces autophagic death and apoptosis.

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History
  • Received:February 18,2021
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  • Online: January 28,2022
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