erastin

However, PRDX4 overexpression showed opposite effects, which were partly reversed by the ferroptosis inhibitor, ferrostatin-1 and the inducer erastin. Most crucially, PRDX4 depletion-mediated inactivation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway could be rescued by 740 Y-P (a PI3K activator), whereas PRDX4 overexpression triggered the activation of the PI3K/AKT signaling pathway, which could be reversed by the PI3K inhibitor LY294002. Collectively, the data suggest that PRXD4 suppresses ferroptosis in ESCC cells by activating the PI3K/AKT signaling pathway, suggesting that targeting PRDX4 may be a novel strategy for treating patients with ESCC.

Clinically, genetic silencing of UBE2C induces ferroptosis and sensitizes tumor cells to the ferroptosis inducer erastin, revealing a therapeutically exploitable vulnerability in MYCN-amplified malignancies. Our study reveals a previously unrecognized MYCN-UBE2C-TFRC-ferroptosis regulatory axis that drives neuroectodermal tumor growth. These findings establish a mechanistic rationale for combining UBE2C silencing and ferroptosis induction as a precision therapeutic strategy against MYCN-amplified tumors.

The study demonstrated that COL11A1 exerts its oncogenic effects by suppressing autophagy via the AKT/Beclin 1 pathway, consequently inhibiting ferroptosis in pancreatic cancer cells. These findings reveal a novel molecular mechanism through which COL11A1 promotes tumor progression and provide a potential therapeutic target for pancreatic cancer treatment.

TRIM31 promotes ESCC progression by degrading VDAC1 and suppressing ferroptosis. Targeting TRIM31 enhances ferroptosis-based therapy and represents a novel, clinically actionable strategy for ESCC treatment. Antioxid. Redox Signal. 44, 550-571.

The effects of NUPR1 knockdown on GSH, ROS, lipid peroxidation, iron, and MDA levels were comparable to those observed after erastin treatment...Notably, the effects of NUPR1 overexpression were partially reversed by the LCN2 knockdown. These findings suggest a significant association between NUPR1 and LCN2, indicating that NUPR1 may serve as a potential therapeutic target for CRC treatment.

We also demonstrated that chemical inhibition of these proteins using RSL3 (GPX4 inhibitor) and erastin (xCT inhibitor) significantly suppressed osteosarcoma cell growth. Collectively, our findings reveal that GPX4 inhibition initiates ferroptosis while simultaneously activating NRF2-driven antioxidant defenses, iron homeostasis mechanisms, and adaptive cell survival signaling. The results highlight potential therapeutic strategies that combine GPX4 inhibition with targeted disruption of compensatory pathways to overcome ferroptosis resistance in osteosarcoma.

The AR antagonist enzalutamide sensitises AR expressing melanoma cells to RSL3 and erastin independent of phenotype state, but in FAOhigh BRAFi relapsed tumours AR up-regulation correlates with the undifferentiated/neural-crest like (UD/NC) state, and enzalutamide synergises with ranolazine in ferroptosis-induction in UD/NC cells. Thus, therapeutically combining ranolazine with the AR inhibitor enzalutamide to induce ferroptosis can circumvent dedifferentiation related BRAFi resistance and could increase therapeutic activity and long-term efficacy.

In vivo, NSUN2 depletion potentiated the antitumor activity of OXA in SW480 xenografts, and combining OXA with the ferroptosis inducer imidazole ketone erastin (IKE) further reduced tumor burden compared with OXA alone, accompanied by increased tumor MDA levels. DHODH restoration rescued ferroptosis and reversed the enhanced drug sensitivity induced by NSUN2 knockdown. These findings identify an NSUN2-DHODH epitranscriptomic axis that promotes CRC progression and OXA resistance by limiting ferroptosis, supporting NSUN2-targeting and ferroptosis-inducing strategies to improve chemotherapy response.

NFIB knockout enhances erastin-induced ferroptosis, marked by elevated Fe2 +, MDA, and ROS levels...In vivo, combined NFIB suppression and ferroptosis induction significantly inhibit tumor growth and increase lipid peroxidation in CRPC xenografts. These findings uncover a critical role of NFIB phase separation and acetylation in ferroptosis regulation and suggest NFIB as a promising therapeutic target in CRPC.

Collectively, these findings establish SLC3A2 as playing a vital oncogenic role in BC tumorigenesis and progression. Its function in inhibiting ferroptosis-especially during cisplatin-based chemotherapy-makes it a promising therapeutic target.

In vitro, ferroptosis was induced in an L929-HaCaT co-culture system using erastin/RSL3, and cells were treated with various concentrations of Rb1. Rb1 functions as an SIRT1-AMPK activator that inhibits ferroptosis and inflammation to promote PI wound healing. These findings underpin the efficacy of Rb1 as a promising multi-target therapeutic candidate for future clinical development.

In vitro, DPP4 overexpression in PDAC cell lines inhibited cell proliferation, induced G1-S cell cycle arrest, impaired mitochondrial respiration, and markedly sensitized cells to erastin-induced ferroptosis...ACSL4 knockdown rescued DPP4 overexpression-induced ferroptosis and lipid ROS accumulation. These results demonstrate that DPP4 acts as a positive regulator of ferroptosis in PDAC by stabilizing ACSL4, highlighting the DPP4-ACSL4 axis as a potential therapeutic target to enhance ferroptosis-based strategies against this aggressive cancer.