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Gastric cancer is a leading global malignancy with high incidence and mortality rates, highlighting the urgent need for novel therapeutic agents. As a natural product in the traditional Chinese medicine Arnebiae Radix, the anti-gastric cancer effects of β,β-dimethylacrylalkannin (β,β-DAL) have not been reported. This study aimed to evaluate the in vitro anti-gastric cancer effects of β,β-DAL and elucidate its underlying mechanisms. Through CCK-8 assay, colony formation experiment, and EdU staining, we demonstrated that β,β-DAL significantly suppressed the proliferation of human gastric cancer AGS and HGC-27 cells in a dose-dependent manner, with 48-hour IC50 values of approximately 0.28 and 0.15 μmol·L-1, respectively. RNA sequencing analysis indicated that the anti-gastric cancer effect of β,β-DAL is associated with the regulation of ferroptosis. Flow cytometry analysis revealed that β,β-DAL upregulated the ROS levels in AGS and HGC-27 cells. In addition, β,β-DAL increased the level of lipid peroxidation in AGS and HGC-27 cells, and the ferroptosis inhibitor ferrostatin-1 reduced their sensitivity to β,β-DAL. Western blot analysis showed that β,β-DAL downregulated the protein expression of stearoyl-CoA desaturase 1 (SCD1) and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as inhibited the ratio of SCD1 to acyl-CoA synthetase long-chain family member 4 (ACSL4) in human gastric cancer AGS and HGC-27 cells. In summary, β,β-DAL may exert anti-gastric cancer effects by inducing ferroptosis in human gastric cancer cells through upregulating ROS levels, increasing intracellular lipid peroxidation, and inhibiting the antioxidant SCD1/Nrf2 pathway. This study provides a candidate drug for gastric cancer treatment and lays the groundwork for further research into the anti-gastric cancer effects of β,β-DAL.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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