RETRACTED: Sulforaphane triggers iron overload-mediated ferroptosis in gastric carcinoma cells by activating the PI3K/IRP2/DMT1 pathway

Abstract

Objective Increasing evidence indicates that prolonged exposure to sulforaphane (SFN) can improve malignancies. However, the role of iron in SFN-triggered death in gastric carcinoma cells and the underlying molecular mechanisms remain unclear. Thus, the current study explored the effects of SFN on iron overload-mediated ferroptosis and the PI3K/IRP2/DMT1 pathway in gastric carcinoma cells. Methods We utilized the MGC-803 cell line to assess whether SFN affected iron metabolism and whether this effect contributed to cell death. Pharmacological inhibition of iron metabolism also was performed to determine the molecular mechanism underlying SFN-triggered iron overload and the disturbance in iron metabolism. Results Our data revealed that SFN treatment altered iron homeostasis and led to iron overload in vitro. Interestingly, SFN-stimulated cell death resulted from ferroptosis, a recently identified iron-dependent form of regulated cell death. Furthermore, an iron chelator, deferiprone, ameliorated the SFN-triggered mitochondrial dysfunction and reduced the iron overload. In addition, we found that the SFN-triggered iron overload was regulated by the PI3K/IRP2/DMT1 signaling pathway. Conclusion We discovered that disturbance in iron metabolism might be involved in the SFN-triggered cell death in gastric carcinoma cells. Blockade of the PI3K/IRP2/DMT1 axis could provide a feedback effect on SFN-induced ferroptosis to protect tumor cells from growth.

Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived

“…Meanwhile, SFN also increased the opening of mitochondrial permeability transition pore in gastric cancer cells. It promotes the entry of iron into mitochondria, leading to Fe 2+ accumulation, mitochondrial dysfunction, and ferroptosis in gastric cancer cells (Wen et al 2023 ).…”

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

“…During ferroptosis, highly reactive free radicals are generated by iron, which cause lipid peroxidation and damage to the cell membrane [226][227][228][229][230][231][232][233][234][235][236][237][238]. In this context, chelating drugs [239][240][241], other chelators, iron [242][243][244][245][246] and related metabolic pathways [247][248][249] and associated biomolecules [250][251][252][253][254][255] can play a major role in the modulation of ferroptosis and influence the treatment of all associated diseases. Similar considerations and interests are also developed by clinical scientists working on microbial diseases, where iron appears to be a major component and regulator of microbial growth, and in this context chelating drugs can play an important role in antimicrobial treatments [256][257][258][259][260].…”