College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang, China.
Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, China.
J Food Sci. 2024 Jul;89(7):4469-4479. doi: 10.1111/1750-3841.17137. Epub 2024 Jun 5.
This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate-functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. PRACTICAL APPLICATION: In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.
本研究旨在评估硫酸软骨素功能化硒纳米粒子（SeCS）的抗宫颈癌活性，并阐明其作用机制。通过 MTT 测定评估 SeCS 对 HeLa 细胞的细胞毒性作用。通过流式细胞术分析和 Western blot 进一步分析 SeCS 的分子机制。结果表明，SeCS 处理导致 HeLa 细胞增殖呈剂量和时间依赖性抑制。流式细胞术获得的数据表明，SeCS 通过诱导 S 期阻滞和细胞凋亡抑制 HeLa 细胞生长。进一步的机制分析发现，SeCS 下调细胞周期蛋白 A 和 CDK2 的表达水平，上调 p21 的表达，导致 S 期阻滞。此外，SeCS 增加 Bax 的水平，降低 Bcl-2 的表达，导致细胞色素 C 从线粒体释放，并激活 caspase-3/8/9 进行 caspase 依赖性凋亡。同时，SeCS 处理后细胞内活性氧（ROS）水平升高，表明 ROS 可能是 SeCS 诱导的 S 期阻滞和细胞凋亡的上游信号。这些数据表明，SeCS 具有抗肿瘤作用，有可能成为癌症患者的新型治疗剂或辅助治疗剂。实际应用：在我们之前的研究中，我们使用硫酸软骨素稳定纳米硒以获得 SeCS，以提高纳米硒的生物活性和稳定性。我们发现它对 HeLa 细胞具有抑制作用。然而，其分子机制尚不清楚。本研究阐明了 SeCS 对 HeLa 细胞损伤的机制。SeCS 有可能成为癌症患者的新型治疗剂或辅助治疗剂。
