Department of Biopharmaceutical Engineering, Dongguk University-WISE, Gyeongju 38066, Gyeongbuk, Republic of Korea.
Int J Mol Sci. 2023 Mar 16;24(6):5661. doi: 10.3390/ijms24065661.
Saikosaponin A is a triterpene saponin and a potentially bioactive compound derived from L. However, the molecular mechanisms and effects of saikosaponin A in gastric cancer remain unknown. In the present study, I evaluated the effects of saikosaponin A on cell death and endoplasmic reticulum stress via calcium and reactive oxygen species release. Targeting reactive oxygen species with diphenyleneiodonium and N-acetylcysteine inhibited cell death and protein kinase RNA-like ER kinase signaling pathway by down-regulating Nox4 and inducing glucose-regulated protein 78 exosomes. Furthermore, saikosaponin A caused a synergistic inhibitory effect of the epithelial mesenchymal transition phenomenon, indicating the reversible phenotype modulation by epithelial cells under radiation exposure in radiation-resistant gastric cancer cells. These results suggest that saikosaponin A-mediated calcium and reactive oxygen species-induced endoplasmic reticulum stress overcome radio-resistance and induce cell death under radiation in gastric cancer cells. Therefore, saikosaponin A in combination with radiation may be a potential strategy for gastric cancer therapy.
柴胡皂苷 A 是一种三萜皂苷，是从 L. 衍生而来的潜在生物活性化合物。然而，柴胡皂苷 A 在胃癌中的分子机制和作用尚不清楚。在本研究中，我们通过钙和活性氧（ROS）的释放来评估柴胡皂苷 A 对细胞死亡和内质网应激的影响。用二苯乙烯碘和 N-乙酰半胱氨酸靶向 ROS，通过下调 Nox4 和诱导葡萄糖调节蛋白 78 外泌体来抑制细胞死亡和蛋白激酶 RNA 样内质网激酶信号通路。此外，柴胡皂苷 A 导致上皮-间充质转化现象的协同抑制作用，表明辐射抗性胃癌细胞中辐射下上皮细胞的可逆表型调节。这些结果表明，柴胡皂苷 A 介导的钙和活性氧诱导的内质网应激可克服放射抵抗，并在胃癌细胞的放射下诱导细胞死亡。因此，柴胡皂苷 A 联合放射治疗可能是胃癌治疗的一种潜在策略。
