Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway

Liu, Yawen; Huang, Pu; Zheng, Li; Xu, Chunhui; Wang, Huizhi; Jia, Baoqing; Gong, Aihua; Xu, Min

doi:10.1155/2022/5361241

Cited by 20 publications

(19 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the BC panel, GSTK1, which is an antioxidant contained in peroxisomes, correlated with low VitC sensitivity, and has been found to be involved in ferroptosis together with CAT, SOD1 and PRDX5(74). This cancer cell death process has been linked to VitC anti-cancer effect in several recent studies and may be further studied(75,76).…”

Section: Discussionmentioning

confidence: 99%

Large pan-cancer cell screen coupled to (phospho-)proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Vallés-Martí,

Böttger,

Yau

et al. 2023

Preprint

View full text Add to dashboard Cite

Increasing preclinical and clinical evidence has positioned high-dose vitamin C as a promising anti-cancer treatment that merits more clinical attention. Multiple cytotoxicity mechanisms have been described, including pro-oxidant effects. To contribute to the preclinical understanding of the broad pan-cancer effects of high-dose vitamin C in a global manner, we determined the IC50 of a large panel of cancer cell lines (n=51) representing 7 solid tumour types and generated proteome data. The majority of cell lines were highly sensitive (IC50 range 0.036-10mM, mean 1.7 ± 0.4 mM), well below a clinically achievable dose. The proteome data (>5000 proteins per sample), showed that high sensitivity is associated with proliferation, as indicated by functional enrichment of cell cycle, RNA splicing and chromatin organization, while lower sensitivity is linked to extracellular vesicles, glycolysis, fatty acid metabolism and mitochondria. Moreover, (phospho-)proteome analysis of on-treatment vitamin C effects on four pancreatic ductal adenocarcinoma (PDAC) cells dosed at a range of IC50 values (Hs766 T, 2 mM; Capan-2, 0.6 mM; PANC-1, 0.14 mM and Suit-2, 0.1 mM) revealed, next to cell line specific effects, down-modulation of AKT-MTOR signalling and immune suppressive signalling, while IFN-α response was enhanced upon vitamin C. Altogether, our comprehensive pharmacological and (phospho-)proteome analysis is the first to assess cancer vulnerabilities and effects of vitamin C on a large cancer cell line panel and underscores the potential of high-dose vitamin C as an anti-cancer agent.

show abstract

Section: Discussionmentioning

confidence: 99%

Large pan-cancer cell screen coupled to (phospho-)proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Vallés-Martí,

Böttger,

Yau

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, natural products such as vitamins, coumarins, and unsaturated fatty acids are considered potential ferroptosis inducers in cancer cells (Y. Liu, Huang, et al, 2022; Vermonden et al, 2021; Xiu et al, 2023). Vitamin C increased intracellular iron levels by promoting ferritin degradation (X. Wang, Xu, et al, 2021).…”

Section: Regulation Of Ferroptosis By Natural Productsmentioning

confidence: 99%

Ferroptosis: Potential opportunities for natural products in cancer therapy

Nie,

Shen,

Zhou

et al. 2023

Phytotherapy Research

View full text Add to dashboard Cite

Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

show abstract

“…Nevertheless, Wang et al were able to demonstrate the induction of ferroptosis by high-dose ascorbate in anaplastic thyroid cancer cells [ 80 ]. Furthermore, it could be shown that ascorbate-induced accumulation of iron in combination with a simultaneous GSH reduction resulted in the enhancement of erastin-induced ferroptosis in pancreatic cancer cells [ 81 ].…”

Section: Generation Of Reactive Oxygen Species and Intracellular Toxi...mentioning

confidence: 99%

Relevant Membrane Transport Proteins as Possible Gatekeepers for Effective Pharmacological Ascorbate Treatment in Cancer

et al. 2023

View full text Add to dashboard Cite

Despite the increasing number of newly diagnosed malignancies worldwide, therapeutic options for some tumor diseases are unfortunately still limited. Interestingly, preclinical but also some clinical data suggest that the administration of pharmacological ascorbate seems to respond well, especially in some aggressively growing tumor entities. The membrane transport and channel proteins are highly relevant for the use of pharmacological ascorbate in cancer therapy and are involved in the transfer of active substances such as ascorbate, hydrogen peroxide, and iron that predominantly must enter malignant cells to induce antiproliferative effects and especially ferroptosis. In this review, the relevant conveying proteins from cellular surfaces are presented as an integral part of the efficacy of pharmacological ascorbate, considering the already known genetic and functional features in tumor tissues. Accordingly, candidates for diagnostic markers and therapeutic targets are mentioned.

show abstract

Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway

Cited by 20 publications

References 53 publications

Large pan-cancer cell screen coupled to (phospho-)proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Large pan-cancer cell screen coupled to (phospho-)proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Ferroptosis: Potential opportunities for natural products in cancer therapy

Relevant Membrane Transport Proteins as Possible Gatekeepers for Effective Pharmacological Ascorbate Treatment in Cancer

Contact Info

Product

Resources

About