Scoulerine, an isoquinoline alkaloid isolated from Corydalis plants, has been reported to possess potent anti-proliferative and pro-apoptotic function in cancer cells. However, the effects and underlying mechanisms of scoulerine on colorectal cancer (CRC) progression remain elusive. CCK-8 and LDH assays were used to evaluate cell viability. Apoptosis was assessed by flow cytometry analysis, caspase-3/7 activity assay, and Western blot analysis of Bax, Bcl-2 and cytochrome c (Cyt C) expression. Oxidative stress level was examined by measuring reactive oxygen species (ROS) and glutathione (GSH) contents and superoxide dismutase (SOD) activity. Endoplasmic reticulum (ER) stress activation was detected by Western blot analysis of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression. Results showed that scoulerine dose-dependently suppressed CRC cell viability. Scoulerine induced apoptosis and increased caspase-3/7 activity in CRC cells. Bax and cytosolic Cyt C expression was enhanced while Bcl-2 and mitochondrial Cyt C expression was reduced in scoulerine-treated CRC cells. Additionally, scoulerine induced oxidative damage in CRC cells by increasing ROS generation and reducing GSH content and SOD activity. Scoulerine activated ER stress, as evidenced by the increased GRP78 and CHOP expression in CRC cells. Interestingly, blocking ROS production by ROS scavenger N-acetyl-cysteine (NAC) attenuated scoulerine-induced ER stress. Inhibition of ER stress by 4-phenyl butyric acid (4-PBA) abolished scoulerine-induced ROS generation in CRC cells. Blockage of ROS and ER stress attenuated scoulerine-induced cell viability reduction and apoptosis in CRC cells. In conclusion, scoulerine promoted cell viability reduction and apoptosis by activating ROS-dependent ER stress in CRC cells.

Scoulerine是一种从延胡索植物中分离出来的异喹啉生物碱，据报道在癌细胞中具有强大的抗增殖和促凋亡功能。然而，苦瓜碱对结直肠癌（CRC）进展的影响和潜在机制仍然难以捉摸。CCK-8和LDH分析用于评估细胞活力。通过流式细胞仪分析，caspase-3 / 7活性测定以及Bax，Bcl-2和细胞色素c的Western印迹分析评估凋亡（Cyt C）表达式。通过测量活性氧（ROS）和谷胱甘肽（GSH）含量以及超氧化物歧化酶（SOD）活性来检查氧化应激水平。内质网（ER）应力激活通过蛋白质印迹分析葡萄糖调节蛋白78（GRP78）和C / EBP同源蛋白（CHOP）表达进行检测。结果表明苦瓜碱剂量依赖性地抑制了CRC细胞的活力。Scoulerine诱导CRC细胞凋亡并增加caspase-3 / 7活性。在苦参碱处理的CRC细胞中，Bax和胞质Cyt C表达增强，而Bcl-2和线粒体Cyt C表达降低。另外，苦瓜碱通过增加ROS的产生并降低GSH含量和SOD活性来诱导CRC细胞的氧化损伤。鞘脂激活ER应激，CRC细胞中GRP78和CHOP表达的增加证明了这一点。有趣的是，通过ROS清道夫N-乙酰半胱氨酸（NAC）阻止ROS的产生减弱了苦参碱诱导的ER应激。4-苯基丁酸（4-PBA）抑制ER应激消除了苦瓜碱诱导的CRC细胞中的ROS生成。ROS和ER应力的阻断减弱了cuulerine诱导的CRC细胞的细胞活力降低和凋亡。总之，苦瓜碱通过激活CRC细胞中ROS依赖的ER应激来促进细胞活力的降低和凋亡。ROS和ER应力的阻断减弱了cuulerine诱导的CRC细胞的细胞活力降低和凋亡。总之，苦瓜碱通过激活CRC细胞中ROS依赖的ER应激来促进细胞活力的降低和凋亡。ROS和ER应力的阻断减弱了cuulerine诱导的CRC细胞的细胞活力降低和凋亡。总之，苦瓜碱通过激活CRC细胞中ROS依赖的ER应激来促进细胞活力的降低和凋亡。