{BiW<sub>8</sub>O<sub>30</sub>} Exerts Antitumor Effect by Triggering Pyroptosis and Upregulating Reactive Oxygen Species
Di Jia, Lige Gong, Ying Li, Shu Cao, Weiming Zhao, Lijun Hao, Shasha Li, Bo Pang, Chunjing Zhang, Shuyan Li, Wei Zhang, Tianyi Chen, Limin Dong, Baibin Zhou, Dan Yang
Abstract
Abstract We successfully synthesized {BiW 8 } , a 10‐nuclear heteroatom cluster modified {BiW 8 O 30 }. At 24 h post‐incubation, the IC 50 values of {BiW 8 } 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 50 value of {BiW 8 } 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 8 }. {BiW 8 } 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 8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.