{BiW8O30} Exerts Antitumor Effect by Triggering Pyroptosis and Upregulating Reactive Oxygen Species. (20th August 2021)

• Record Type: Journal Article
• Authors: Jia, Di; Gong, Lige; Li, Ying; Cao, Shu; Zhao, Weiming; Hao, Lijun; Li, Shasha; Pang, Bo; Zhang, Chunjing; Li, Shuyan; Zhang, Wei; Chen, Tianyi; Dong, Limin; Zhou, Baibin; Yang, Dan
• Is Part Of: Angewandte Chemie. Volume 133:Number 39(2021)
• Page Start: 21619
• Page End: 21626
• Publication Date: 2021-08-20
• Subjects: {BiW8O30} -- antitumor mechanism -- pyroptosis -- ROS -- transcriptome analysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202107265
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: We successfully synthesized {BiW8 }, a 10‐nuclear heteroatom cluster modified {BiW8 O30 }. At 24 h post‐incubation, the IC50 values of {BiW8 } 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 IC50 value of {BiW8 } 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 {BiW8 }. {BiW8 } 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 {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair. Abstract : We successfully synthesized {BiW8 }, a 10‐nuclear heteroatom cluster modified {BiW8 O30 }. {BiW8 } suppressed the proliferation, migration, and invasion of MG63 cells. We identified POM‐induced pyroptosis for the first time. Decreased GSH content and increased ROS levels were observed in {BiW8 } ‐treated cells. {BiW8 } executed multiple antitumor mechanisms, such as activation of pyroptosis, regulation of oxidative stress, and inhibition of DNA repair.