Α-Solanine induces ferroptosis in nasopharyngeal carcinoma via targeting HSP90α/p53 axis. (May 2023)

• Record Type: Journal Article
• Authors: Cui, Xuehui; Gong, Yitong; Ge, Jun; Feng, Xiaofei; Xiong, Xuemei; Shi, Zhen; Zheng, Qiusheng; Li, Defang; Bi, Sixue
• Is Part Of: Journal of functional foods. Volume 104(2023)
• Publication Date: 2023-05
• Subjects: Nasopharyngeal carcinoma -- α-Solanine -- Ferroptosis -- HSP90α -- p53; BCA bicinchoninic acid -- CMA chaperone-mediated autophagy -- CoIP Co-immunoprecipitation -- DARTS drug affinity responsive target stability -- DEGs differentially expressed genes -- DMEM dulbecco's modified eagle medium -- DMSO dimethyl sulfoxide -- FBS fetal bovine serum -- Fer-1 Ferrostatin-1 -- GPX4 glutathione peroxidase 4 -- HE haematoxylin and eosin -- HSP90α heat shock protein 90α -- IC50 half maximal inhibitory concentration -- IHC immunohistochemistry -- IPA Ingenuity Pathway Analysis -- MDA malondialdehyd -- MTT 3-(4, 5-dimethylthia-zol-2-yl)-2, 5-diphenyltetrazolium bromide -- NPC Nasopharyngeal carcinoma -- PBS phosphate buffered saline -- PTGS2 prostaglandin-endoperoxide synthase 2 -- ROS reactive oxygen species -- RT room temperature -- SDS/PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- SLC7A11 solute carrier family 7, member 11 -- TEM transmission electron microscope -- WB Western blotting; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2023.105517
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: α-Solanine can induce ferroptosis in NPC HK-1and 5-8F cells. HSP90α was the direct target of α-solanine action in NPC HK-1 and 5-8F cells. HSP90α/p53 axis was highly involved in α-solanine-mediated ferroptosis. α-Solanine-mediated tumor suppression in vivo was associated with ferroptosis. Abstract: α-Solanine, a natural small molecule compound, mainly derived from potato tubers with anti-tumor and anti-inflammatory effects. No studies have yet confirmed that α-solanine can act on tumor cells via ferroptosis, and its molecular mechanism is unclear. The present study aimed to study whether α-solanine could induce nasopharyngeal carcinoma (NPC) cell death through ferroptosis and its specific molecular mechanism. Here, α-solanine was proven to trigger ferroptosis in NPC cells via targeting HSP90α directly. The primary manifestations of α-solanine-induced ferroptosis in NPC HK-1 and 5-8F cells were increased levels of ROS, MDA, iron and altered mitochondrial structure. Moreover, there was a noticeable decrease in SLC7A11 and GPX4 expression. Mechanistic study showed that α-solanine directly binds to HSP90α which promotes p53 expression and ultimately inhibits the level of SLC7A11 to inactivate GPX4. Collectively, our study revealed the potential application of α-solanine in the treatment of nasopharyngeal carcinoma through ferroptosis.