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Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity

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Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Published:18 October 2021 DOI: 10.1155/2021/1783485 PMID: 34707773
Yi Luo, Xu Gao, Luetao Zou, Miao Lei, Junming Feng, Zhenming Hu

Abstract

Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

Substances (24)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 248 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 248 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 248 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 248 suppliers $10.00-$2822.00
BAVACHIN 19879-32-4 C20H20O4 221 suppliers $11.00-$1350.00
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1,8-Diazafluoren-9-one 54078-29-4 C11H6N2O 212 suppliers $19.00-$68579.00
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