Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

Lü, Yi; Mao, Jinbao; Xu, Yanyan; Pan, Hao; Wang, Yu; Li, Wei

doi:10.1177/09603271221120652

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Galangin treatment significantly rescued the phosphorylation levels of PI3K and AKT, and the anti-ferroptosis of galangin could be counteracted by the PI3K inhibitor LY294002 (Chen et al 2022 ). Meanwhile, Lu et al found that ropivacaine could inhibit the PI3K-AKT pathway to promote ferroptosis in ovarian cancer cells (Lu et al 2022 ). Liu et al found that the reduction of NRF2 induced by CdTe QDs leads to the ERK1/2 phosphorylation, which activated ferritinophagy and caused the degradation of FTH1 in lysosomes and proteasomes.…”

Section: Discussionmentioning

confidence: 99%

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Zhao,

Yu,

Yin

et al. 2024

Inflammopharmacol

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Objective Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. Methods CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund’s adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. Results The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. Conclusions Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.

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Section: Discussionmentioning

confidence: 99%

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Zhao,

Yu,

Yin

et al. 2024

Inflammopharmacol

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“…In addition, we detected the expression of ferroptosisrelated proteins, and demonstrated that ropivacaine combined with cisplatin increased the ferroptosis levels of LOVO and LOVO/DDP cells via downregulating Nrf-2, GPX4 and SLC7A11 proteins when compared to cisplatin alone treatment, we also found the accumulation of Fe2+ was elevated in combination with ropivacaine and cisplatin. Furthermore, a study conducted by Lu et al reported that ropivacaine could directly induce ferroptosis in ovarian cancer cells to restrain the cell stemness [42].…”

Section: Discussionmentioning

confidence: 99%

Ropivacaine enhanced the cisplatin-sensitivity of Human colorectal cancer cells by accelerating ROS-meditated apoptosis and ferroptosis

Zhang

Zeng

Zhao

et al. 2023

Preprint

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The failure of cisplatin treatment to human colorectal cancer due to cisplatin-sensitivity reduced, it’s necessary to find the new adjuvant agents to increase the cisplatin-sensitivity. Ropivacaine has been demonstrated to inhibit the proliferation and migration of variety of cancer cells, however, it remains unclear whether it could increase the cisplatin sensitivity of colorectal cancer cells. The cisplatin-resistant cell line for colorectal cancer named LOVO/DDP cells were established by repeated induction of different concentration of cisplatin, the cell viability, proliferation, migration, and apoptosis were assessed by Colony-forming assay, Transwell assay, Wound Healing and Annexin V/PI flow cytometry; JC-1 and ROS detection kits were used to determine the levels of mitochondrial membrane potential and reactive oxygen species (ROS). The expression of MMP-9, Nrf-2, GPX4, SLC7A11, SIRT1 proteins were detected by Western-blot and immunofluorescence. Compared with the control group, the activity of LOVO cells decreased significantly and that in LOVO/DDP cells decreased slightly with the increase of cisplatin. After the treatment of ropivacaine combined with cisplatin, the LOVO/DDP cells viability was significantly decreased than cisplatin alone (P<0.01). Compared with cisplatin alone treatment group, the proliferation and migration of LOVO cells and LOVO/DDP cells were significantly reduced in combined group. Ropivacaine combined with cisplatin enhanced apoptosis, the production of ROS, induced mitochondrial dysfunction, and down-regulated anti-ferroptosis and SIRT1 proteins. Those above results demonstrated that ropivacaine could increase the chemosensitivity of cisplatin-resistant human colon cancer cells, and its mechanism may be through promoting cancer cell apoptosis and ferroptosis.

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“…Lastly, some evidence suggests that anesthetics can also possess anti-cancer properties by inducing ferroptosis ( Abudurousuli et al, 2023 ). This becomes more intriguing when inhibiting PI3K/Akt by local anesthetic agents, such as bupivacaine and ropivacaine, can trigger these ferroptotic changes ( Hao et al, 2022 ; Lu et al, 2022 ). This signaling pathway appears to function as a central regulatory pathway for controlling ferroptosis in cancer cells.…”

Section: Targeting Pi3k/akt To Induce Ferroptosismentioning

confidence: 99%

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Su,

Peng,

Liu

2024

Front. Cell Dev. Biol.

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The global challenge posed by cancer, marked by rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. The PI3K/Akt signaling pathway, frequently amplified in various cancers, is central in regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, and resistance to therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized by iron-dependent processes and lipid reactive oxygen species buildup, holds implications for diseases, including cancer. Exploring the interplay between the dysregulated PI3K/Akt pathway and ferroptosis unveils potential insights into the molecular mechanisms driving or inhibiting ferroptotic processes in cancer cells. Evidence suggests that inhibiting the PI3K/Akt pathway may sensitize cancer cells to ferroptosis induction, offering a promising strategy to overcome drug resistance. This review aims to provide a comprehensive exploration of this interplay, shedding light on the potential for disrupting the PI3K/Akt pathway to enhance ferroptosis as an alternative route for inducing cell death and improving cancer treatment outcomes.

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Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

Cited by 11 publications

References 38 publications

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Ropivacaine enhanced the cisplatin-sensitivity of Human colorectal cancer cells by accelerating ROS-meditated apoptosis and ferroptosis

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

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