UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death

Arslanbaeva, Liaisan; Tosi, Giovanni; Ravazzolo, Marco; Simonato, Manuela; Tucci, Francesco; Pece, Salvatore; Cogo, Paola; Santoro, Massimo

doi:10.1016/j.redox.2022.102272

Cited by 19 publications

(16 citation statements)

References 59 publications

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“…On the other hand, melanoma cells have high reactive oxygen species (ROS) levels and a more robust antioxidant defense system than melanocytes. Scientific research indicates that melanoma cells have efficient mechanisms involved in antioxidant defense, such as the activation of the nuclear factor erythroid 2–related factor 2 (NRF2) and a higher level of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) [ 74 ]. The formation of NADPH in cells is related to the pentose pathway.…”

Section: Resultsmentioning

confidence: 99%

“…NADPH contributes to regenerating reduced glutathione and ROS production through NADPH oxidases catalyzing electron transfer from the NADPH molecule to molecular oxygen, thus maintaining the redox balance. Paudel et al found that melanoma cells with reduced sensitivity to BRAF inhibitor exhibit an enhanced anti-oxidation and redox buffer capacity, specifically through NADPH oxidizing enzymes [ 74 ]. Thus, the lowest activity against A375 could be related to being more resistant to ROS generation.…”

Section: Resultsmentioning

confidence: 99%

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Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells

Łażewski

Kucińska

Potapskiy

et al. 2022

IJMS

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This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1H and 13C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up to 0.54. The photodynamic activity was tested using bladder (5637), prostate (LNCaP), and melanoma (A375) cancer cell lines. In vitro experiments clearly showed the structure–activity relationship regarding types of substituents, their positions in the phenyl ring, and the variety of central metal ions on the porphyrin core. Notably, the metal-free derivative 3 and its zinc derivative 6 exerted strong cytotoxic activity toward 5637 cells, with IC50 values of 8 and 15 nM, respectively. None of the tested compounds induced a cytotoxic effect without irradiation. In conclusion, these results highlight the potential value of the tested compounds for PDT application.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells

Łażewski

Kucińska

Potapskiy

et al. 2022

IJMS

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“…UBIAD1 has been known as a tumor suppressor for urological cancer, castrate-resistant prostate cancer and renal cell carcinoma ( Fredericks et al, 2013 ). Also, the role of UBIAD1 in synthesis of non-mitochondrial CoQ10 was beneficial for the melanoma cells since it prevented lipid peroxidation and cell death ( Arslanbaeva et al, 2022 ). It is speculated that the UBIAD1 product, MK-4, has a beneficial role in the protection of diverse types of cancer, however an in-depth investigation is needed in these areas.…”

Section: Conclusion and Future Scopementioning

confidence: 99%

Synthesis, function, and regulation of sterol and nonsterol isoprenoids

Faulkner

2022

Front. Mol. Biosci.

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Cholesterol, the bulk end-product of the mevalonate pathway, is a key component of cellular membranes and lipoproteins that transport lipids throughout the body. It is also a precursor of steroid hormones, vitamin D, and bile acids. In addition to cholesterol, the mevalonate pathway yields a variety of nonsterol isoprenoids that are essential to cell survival. Flux through the mevalonate pathway is tightly controlled to ensure cells continuously synthesize nonsterol isoprenoids but avoid overproducing cholesterol and other sterols. Endoplasmic reticulum (ER)-localized 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (HMGCR), the rate limiting enzyme in the mevalonate pathway, is the focus of a complex feedback regulatory system governed by sterol and nonsterol isoprenoids. This review highlights transcriptional and post-translational regulation of HMGCR. Transcriptional regulation of HMGCR is mediated by the Scap-SREBP pathway. Post-translational control is initiated by the intracellular accumulation of sterols, which causes HMGCR to become ubiquitinated and subjected to proteasome-mediated ER-associated degradation (ERAD). Sterols also cause a subfraction of HMGCR molecules to bind the vitamin K2 synthetic enzyme, UbiA prenyltransferase domain-containing protein-1 (UBIAD1). This binding inhibits ERAD of HMGCR, which allows cells to continuously synthesize nonsterol isoprenoids such as geranylgeranyl pyrophosphate (GGPP), even when sterols are abundant. Recent studies reveal that UBIAD1 is a GGPP sensor, dissociating from HMGCR when GGPP thresholds are met to allow maximal ERAD. Animal studies using genetically manipulated mice disclose the physiological significance of the HMGCR regulatory system and we describe how dysregulation of these pathways contributes to disease.

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“…In order to survive and proliferate, tumor cells possess defense systems to remove LPO. , In recent studies, photodynamic therapy (PDT) and radiotherapy have been proposed to elevate LPO stress for the enhancement of tumor therapeutic effect . However, the activity of reactive oxygen species (ROS) in the tumor could be offset by the dihydroorotate dehydrogenase (R) redox system, resulting in an unsatisfactory therapeutic effect. − R suppresses mitochondrial lipid peroxidation and protects tumor cells from ferroptosis. ,, Thus, the inactivation of R, combined with the treatment of ferroptosis inducers, is speculated to efficiently produce lipid peroxyl radicals, leading to substantial cancer cell ferroptosis for tumor inhibition R …”

Section: Introductionmentioning

confidence: 99%

“…12 In order to survive and proliferate, tumor cells possess defense systems to remove LPO. 13,14 In recent studies, photodynamic therapy (PDT) and radiotherapy have been proposed to elevate LPO stress for the enhancement of tumor therapeutic effect. 9 However, the activity of reactive oxygen species (ROS) in the tumor could be offset by the dihydroorotate dehydrogenase (R) redox system, resulting in an unsatisfactory therapeutic effect.…”

Section: ■ Introductionmentioning

confidence: 99%

Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System

Chen

Yang

Liang

et al. 2023

ACS Appl. Mater. Interfaces

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The upregulation of dihydroorotate dehydrogenase (DHODH) redox systems inside tumor cells provides a powerful shelter against lipid peroxidation (LPO), impeding ferroptosis-induced antitumor responses. To solve this issue, we report a strategy to block redox systems and enhance ferroptotic cancer cell death based on a layered double hydroxide (LDH) nanoplatform (siR/IONs@LDH) co-loaded with ferroptosis agent iron oxide nanoparticles (IONs) and the DHODH inhibitor (siR). siR/IONs@LDH is able to simultaneously release IONs and siR in a pH-responsive manner, efficiently generate toxic reactive oxygen species (ROS) via an Fe 2+ -mediated Fenton reaction, and synergistically induce cancer cell death upon the acceleration of LPO accumulation. In vivo therapeutic evaluations demonstrate that this nanomedicine has excellent performance for tumor growth inhibition without any detectable side effects. This work thus provides a new insight into nanomaterial-mediated tumor ferroptosis therapy.

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UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death

Cited by 19 publications

References 59 publications

Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells

Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells

Synthesis, function, and regulation of sterol and nonsterol isoprenoids

Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System

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