Department of Hematology, The First People's Hospital of Yunnan Province, Kunming, China.
Yunnan Province Clinical Research Center for Hematologic Disease, Kunming, China.
J Biochem Mol Toxicol. 2023 Oct;37(10):e23424. doi: 10.1002/jbt.23424. Epub 2023 Jul 31.
Multiple myeloma (MM) is an incurable cancer that is characterized by malignant plasma cell proliferation. Approximately 10% of all blood cancers are MM, and there is no standard curative therapy. In this work, we intended to synthesize, characterize, and assess the anticancer effects of selenium/chitosan/polyethylene glycol-carvacrol nanocomposites (SCP-Car-NCs) on MM U266 cells in vitro. Various characterization techniques were used to characterize the synthesized SCP-Car-NCs. Several in vitro free radical scavenging experiments were conducted to test the ability of synthesized SCP-Car-NCs to scavenge the different free radicals. The cytotoxicity of SCP-Car-NCs was assessed on Vero and U266 cells using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. By using various fluorescence staining techniques, the amount of reactive oxygen species (ROS) generation, MMP, and apoptosis were measured. Using commercial test kits, the levels of oxidative stress and apoptotic biomarkers in control and treated U266 cells were assessed. The highest peak in the UV spectral analysis was found to be at 271 nm, demonstrating the development of SCP-Car-NCs. Fourier transform infrared analysis showed that the synthesized SCP-Car-NCs contained a variety of stretching and bonding. The X-ray diffraction study confirmed the crystallinity of SCP-Car-NCs. The dynamic light scattering analysis showed that the SCP-Car-NCs had an average size of 171 nm. The different free radicals, such as the 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, and peroxyl radicals, were significantly scavenged by the SCP-Car-NCs. According to the MTT assay results, the SCP-Car-NCs decreased the viability of U266 cells while having no impact on the proliferation of Vero cells. The SCP-Car-NCs significantly boosted ROS production, decreased the MMP level, and promoted apoptosis, as evidenced by the fluorescence staining experiments. In U266 cells treated with SCP-Car-NCs, the level of thiobarbituric acid reactive substances increased while superoxide dismutases and glutathione levels were reduced. In the SCP-Car-NCs treated U266 cells, it was found that the Bax, caspase-3, and -9 activities had increased while the Bcl-2 level had decreased. In conclusion, our findings show that SCP-Car-NCs treatment reduced the viability and increased apoptosis in the U266 cells, providing a new insight on SCP-Car-NCs' potential for usage in the future to treat MM.
多发性骨髓瘤（MM）是一种无法治愈的癌症，其特征是恶性浆细胞增殖。大约 10%的血液癌症是 MM，目前没有标准的治愈疗法。在这项工作中，我们旨在合成、表征硒/壳聚糖/聚乙二醇-香芹酚纳米复合材料（SCP-Car-NCs），并评估其在体外对 MM U266 细胞的抗癌作用。使用各种表征技术对合成的 SCP-Car-NCs 进行了表征。进行了几种体外自由基清除实验，以测试合成的 SCP-Car-NCs 清除不同自由基的能力。使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴化物（MTT）测定法评估 SCP-Car-NCs 对 Vero 和 U266 细胞的细胞毒性。通过使用各种荧光染色技术，测量活性氧（ROS）生成、MMP 和细胞凋亡的量。使用商业测试试剂盒评估对照和处理后的 U266 细胞中氧化应激和凋亡生物标志物的水平。在紫外光谱分析中发现最高峰值出现在 271nm，表明 SCP-Car-NCs 的形成。傅里叶变换红外分析表明，合成的 SCP-Car-NCs 含有多种伸缩和键合。X 射线衍射研究证实了 SCP-Car-NCs 的结晶度。动态光散射分析表明，SCP-Car-NCs 的平均粒径为 171nm。2,2-二苯基-1-苦基肼基、羟基和过氧自由基等不同自由基被 SCP-Car-NCs 显著清除。根据 MTT 测定结果，SCP-Car-NCs 降低了 U266 细胞的活力，而对 Vero 细胞的增殖没有影响。荧光染色实验表明，SCP-Car-NCs 显著增加 ROS 生成，降低 MMP 水平，并促进细胞凋亡。在 SCP-Car-NCs 处理的 U266 细胞中，发现硫代巴比妥酸反应物质的水平增加，而超氧化物歧化酶和谷胱甘肽的水平降低。在 SCP-Car-NCs 处理的 U266 细胞中，发现 Bax、caspase-3 和 -9 的活性增加，而 Bcl-2 的水平降低。总之，我们的研究结果表明，SCP-Car-NCs 处理降低了 U266 细胞的活力并增加了细胞凋亡，为 SCP-Car-NCs 在未来用于治疗 MM 提供了新的见解。
