{BiW(8)O(30)} Exerts Antitumor Effect by Triggering Pyroptosis and Upregulating Reactive Oxygen Species

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.