{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.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)