Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields

Martín‐Sánchez, Diego; Fontecha‐Barriuso, Miguel; Sanchez-Niño, María Dolores; Ramos, Adrián M.; Benavente, R. Cabello; Enguita, C. González; Linkermann, Andreas; Sanz, Ana B.; Ortíz, Alberto

doi:10.1038/s41419-017-0043-2

Cited by 27 publications

(21 citation statements)

References 154 publications

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“…The key genetic inactivations or mutations for RCC include those in MET proto-oncogene (MET), polybromo 1 (PBRM1), transcription factor binding to IGHM enhancer 3 (TFE3), folliculin (FLCN), Tuberous Sclerosis Complex 1 (TSC1), fumarate hydratase (FH), succinate dehydrogenase complex subunit D (SDHD), phosphatase and tensin homolog (PTEN) and VHL [10, 11], which leads to the accumulation of downstream oncogenic targets, such as HIFs [12]. ccRCC develops resistance to apoptosis by diverse mechanisms, including VHL mutations [13]. Various diagnostic, prognostic, treatment and predictive biomarkers associated with angiogenesis in RCC have been used, of which VHL and its downstream HIF/VEGF pathway have been well understood, and associated targeted therapy has also been developed.…”

Section: Targeted Therapy For Mrccmentioning

confidence: 99%

“…The tumor heterogeneity, dynamic variation and crosstalk of numerous cell death-related signaling pathways, such as phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT), mitogen activated protein kinases (MAPK)/extracellular regulated protein kinases (ERK), and inhibitor of NF-κB (IκB)/nuclear factor-kappa B (NF-κB), may be associated with the resistance of targeted therapy. NF-κB activation is a well-characterized consequence of the HIF-independent VHL deficiency signaling pathway [13, 36]. NF-κB essential modulator (NEMO)-driven VHL/HIF pathway activation is also involved in ccRCC progression [37].…”

Section: Cell Death-related Molecules For Rcc Targeted Therapymentioning

confidence: 99%

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Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy

et al. 2019

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Renal cell carcinoma (RCC) is not sensitive to conventional radio- and chemotherapies and is at least partially resistant to impairments in cell death-related signaling pathways. The hallmarks of RCC formation include diverse signaling pathways, such as maintenance of proliferation, cell death resistance, angiogenesis induction, immune destruction avoidance, and DNA repair. RCC diagnosed during the early stage has the possibility of cure with surgery. For metastatic RCC (mRCC), molecular targeted therapy, especially antiangiogenic therapy (e.g., tyrosine kinase inhibitors, TKIs, such as sunitinib), is one of the main partially effective therapeutics. Various forms of cell death that may be associated with the resistance to targeted therapy because of the crosstalk between targeted therapy and cell death resistance pathways were originally defined and differentiated into apoptosis, necroptosis, pyroptosis, ferroptosis and autophagic cell death based on cellular morphology. Particularly, as a new form of cell death, T cell-induced cell death by immune checkpoint inhibitors expands the treatment options beyond the current targeted therapy. Here, we provide an overview of cell death-related molecules and biomarkers for the progression, prognosis and treatment of mRCC by targeted therapy, with a focus on apoptosis and T cell-induced cell death, as well as other forms of cell death.

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Section: Targeted Therapy For Mrccmentioning

confidence: 99%

Section: Cell Death-related Molecules For Rcc Targeted Therapymentioning

confidence: 99%

Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy

et al. 2019

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“…Future studies will investigate modes of cells deaths such as necrosis, autophagy, necroptosis, and ferroptosis in prostate cancer cells treated with 3-BPA and/or SC-514. 91 The existence of multidrug resistance (MDR) may influence the mode of cell deaths or survival pathways in prostate cancer cells as mentioned above. Metabolic activities of prostate cancer cells favor the sustained production of ATP energy required for MDR ( Figure 2).…”

Section: Nbt Assay Measuring the Ros Levelmentioning

confidence: 99%

Interaction between 3-Bromopyruvate and SC-514 in prostate cancer treatment

Famuyiwa¹,

Jebelli²,

Diaka³

et al. 2018

JCPCR

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Background: Prostate cancer (PCA) is the second most diagnosed cancer in men. The high incidence of prostate cancer has been attributed to failures in single treatment of chemotherapy. Failure of mono treatment is mediated by heterogeneity and plasticity of prostate cancer cells. 3-Bromopyruvate is one of the most common chemotherapeutic drugs used for the treatment of prostate cancer. However, its clinical therapeutic efficiency has been limited due to numerous side effects and drug resistance. SC-514 is a relatively new drug. Very little information exists on the anti-cancer effects of SC-514. Nevertheless, SC-514 might be able to overcome side effects of conventional chemotherapy. 3-BPA is strong potentiators of chemotherapeutic drug. 3-BPA has the potential to potentiate the anti-cancer activity of SC-514. The combination of 3-BPA and SC-514 might be able to inhibit prostate cancer carcinogenesis despite existence of heterogeneity and plasticity of prostate cancer cells. Objective of study: This study aims to investigate the potential interaction between 3-BPA and SC-514 during treatment of prostate cancer. Method: The bioassays used in this study include: trypan blue exclusion, MTT tetrazolium, NBT, LDH cytotoxicity, and poly caspase assay. Combination Index (CI) calculation was used to investigate the antagonistic, synergistic or additive interaction between 3-BPA and SC-514. One-way ANOVA was utilized to compare the cytotoxic effects of 3-BPA, SC-514 and the combination of 3-BPA and SC-514 on DU-145 cells and PC-3 cells prostate cancer cells. Results: Results suggested a weak negative (r=-0.29) to moderate negative (r=-0.42) correlation between ROS released and cell death. In addition, there was a weak correlation (r=0.19) between percentage ROS induced and percentage apoptotic death. There was a positive correlation between the concentration of drug and cell death in DU-145 and PC-3 prostate cancer cells. Conclusion: The overlap in mechanisms of action of 3-BPA and SC-514 increased the impact of SC-514 on prostate cancer cells. Hence, the combination of 3-BPA and SC-514 was more therapeutically effective (synergistic effect) than the single treatments of either 3-BPA or SC-514. The synergistic effect between 3-BPA and SC-514 did not occur by ROS induction.The apoptotic induction in DU-145 and PC-3 prostate cancer cells appears to occur via a mechanism other than reactive species (ROS) induction. This study suggests that the combination of 3-BPA and SC-514 as a therapeutic regimen can inhibit prostate cancer carcinogenesis effectively.

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“…Resistance to current anticancer therapies presents significant unmet medical needs. Induction of selective non-apoptotic cell death might be considered as an effective method for developing more effective therapies against RCC[3].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 represses ER stress-related ferroptosis in renal carcinoma cells via HO-1

Shen

Tian

et al. 2020

Preprint

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Selective-induction of regulated cell death is considered as a useful strategy for developing effective therapies against renal cell carcinoma (RCC). In this study, the role of nuclear factor-E2-related factor 2 (Nrf2) and its downstream genes in erastin-induced ferroptosis of renal carcinoma cells was investigated. Erastin induced endoplasmic reticulum (ER) stress and ferroptosis in renal carcinoma cells (786-0 and Caki-1), which was confirmed by morphological changes, increased lipid oxidation and ferroptosis inhibition. Data obtained from TCGA dataset showed that Nrf2 and heme oxygenase-1 (HO-1) were not only significantly differentially expressed between RCC and normal samples, but also associated with better survival in RCC patients. Moreover, the process of ferroptosis induced by erastin in renal carcinoma cells was accompanied by increased expression of Nrf2 and HO-1. Inhibition of Nrf2 or HO-1 expression enhanced lipid ROS accumulation and ferroptosis. Furthermore, pharmacological activation of HO-1 reversed ferroptosis-sensitizing effect of Nrf2 silencing, thereby clarifying the key role of Nrf2/HO-1 pathway in erastin-induced ferroptosis in renal carcinoma cells. In summary, we identified the role of Nrf2/HO-1 signaling pathway in the protection of renal carcinoma cells from ER stress-related ferroptosis, which indicated that targeting of Nrf2/HO-1 pathway as a viable treatment strategy for RCC. Graphical abstract (supplementary figure):Nrf2 protects against ER stress-related ferroptosis via HO-1 in renal cancer cells.Cystine/glutamate antiporter (SLC7A11) abbreviated as xCT. Mitochondria abbreviated as Mito.

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Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields

Cited by 27 publications

References 154 publications

Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy

Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy

Interaction between 3-Bromopyruvate and SC-514 in prostate cancer treatment

Nrf2 represses ER stress-related ferroptosis in renal carcinoma cells via HO-1

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