Department of Biochemistry and Molecular Biology, Qiqihar Medical University, Qiqihar, 161006, China.
School of Materials Science and Chemical Engineering, Harbin University of Science and Technology, Harbin, 150080, China.
Angew Chem Int Ed Engl. 2021 Sep 20;60(39):21449-21456. doi: 10.1002/anie.202107265. Epub 2021 Aug 20.
We successfully synthesized {BiW }, a 10-nuclear heteroatom cluster modified {BiW O }. At 24 h post-incubation, the IC values of {BiW } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 μM, respectively. The IC value of {BiW } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW }. {BiW } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post-incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.
我们成功合成了{BiW}，一种 10 核杂原子簇修饰的{BiW O}。孵育 24 h 后，{BiW}对 HUVEC、MG63、RD、Hep3B、HepG2 和 MCF7 细胞的 IC50 值分别为 895.8、127.3、344.3、455.0、781.3 和 206.3 μM。{BiW}对 MG63 细胞的 IC50 值比其他原料低 2 倍以上。通过形态学和功能特征，我们证明细胞焦亡是{BiW}诱导细胞死亡的一种新的机制。{BiW}在孵育 24 h 后使 MG63 细胞中的活性氧（ROS）水平增加了 2 倍。与 0 h 相比，孵育 6、12、24、36 和 48 h 后，细胞内谷胱甘肽（GSH）含量分别下降了 59%、65%、75%、94%和 97%。此外，通过转录组分析和化学模拟，我们鉴定了{BiW}的多种抗肿瘤机制，包括细胞焦亡的激活、GSH 生成的抑制、GSH 的消耗以及 DNA 修复的抑制。
