New insights into vitamin K biology with relevance to cancer

Welsh, JoEllen; Bak, Min Ji; Narvaez, Carmen J.

doi:10.1016/j.molmed.2022.07.002

Cited by 29 publications

(22 citation statements)

References 148 publications

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“…UBIAD1 (UbiA Prenyltransferase Domain Containing 1) is a biosynthetic enzyme that converts vitamin K1 (phylloquinone) to menaquinone, which is the most abundant form of vitamin K2 in human tissue (33). Low expression of UBIAD1 in human breast tumours correlates with reduced survival (34), and also associates with risk for bladder cancer (35). TPRG1 encodes for Tumour protein P63 Regulated 1 and its expression is associated with estrogen receptor-positive and triple-negative breast cancers (36, 37).…”

Section: Discussionmentioning

confidence: 99%

Blood-based epigenome-wide analyses on the prevalence and incidence of nineteen common disease states

Hillary

McCartney

Bernabeu

et al. 2023

Preprint

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BackgroundBlood DNA methylation can inform us about the biological mechanisms that underlie common disease states. Previous epigenome–wide analyses of common diseases often focus solely on the prevalence or incidence of individual conditions and rely on small sample sizes, which may limit power to discover disease–associated loci.ResultsWe conduct blood–based epigenome-wide association studies on the prevalence of 14 common disease states in Generation Scotland (nindividuals≤18,413, nCpGs=752,722). We also utilise health record linkage to perform epigenome–wide analyses on the incidence of 19 disease states. We present a structured literature review on existing epigenome–wide analyses for all 19 disease states to assess the degree of replication within the existing literature and the novelty of the present findings. We identify 69 associations between CpGs and the prevalence of four disease states at baseline, of which 58 are novel. We also uncover 64 CpGs that associate with the incidence of two disease states (COPD and type 2 diabetes), of which 56 are novel. These associations were independent from common lifestyle risk factors. We highlight poor replication across the existing literature. Here, replication was defined by the reporting of at least one common gene in >2 studies examining the same disease state. Existing blood–based epigenome–wide analyses showed evidence of replication for only 4/19 disease states (with up–to–15% of unique genes replicated for lung cancer).ConclusionsOur summary data and structured review of the literature provide an important platform to guide future studies that examine the role of blood DNA methylation in complex disease states.

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Section: Discussionmentioning

confidence: 99%

Blood-based epigenome-wide analyses on the prevalence and incidence of nineteen common disease states

Hillary

McCartney

Bernabeu

et al. 2023

Preprint

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“…Recently, increasing attention has been paid to the relationship between vitamin K and malignancy [ 33 ]; several in vivo observational studies have established a relationship between vitamin K intake and cancer mortality [ 33 , 34 ]. An in vitro study also reported that vitamin K retains a peculiar cytotoxicity towards cancer cells through different mechanisms implicated in cell growth arrest and suppression of proliferation [ 33 ]. Taking these observations into account, all the products developed following vitamin K absence, such as PIVKA-II, acquire a new role in the management of cancer.…”

Section: Discussionmentioning

confidence: 99%

PANC-1 Cell Line as an Experimental Model for Characterizing PIVKA-II Production, Distribution, and Molecular Mechanisms Leading to Protein Release in PDAC

Farina,

Tartaglione,

Preziosi

et al. 2024

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence (PIVKA-II) is a protein increased in various cancers (particularly in hepatocellular carcinoma), and it has recently exhibited superior diagnostic performance in PDAC detection compared to other biomarkers. The aim of our research was to identify an in vitro model to study PIVKA-II production, distribution, and release in PDAC. We examined the presence of PIVKA-II protein in a panel of stabilized pancreatic cancer cell lines by Western blot analysis and indirect immunofluorescence (IFA). After quantitative evaluation of PIVKA-II in PaCa 44, H-Paf II, Capan-1, and PANC-1, we adopted the latter as a reference model. Subsequently, we analyzed the effect of glucose addiction on PIVKA-II production in a PANC-1 cell line in vitro; PIVKA-II production seems to be directly related to an increase in glucose concentration in the culture medium. Finally, we evaluated if PIVKA-II released in the presence of increasing doses of glucose is concomitant with the expression of two well-acknowledged epithelial–mesenchymal transition (EMT) markers (Vimentin and Snail). According to our experimental model, we can speculate that PIVKA-II release by PANC-1 cells is glucose-dependent and occurs jointly with EMT activation.

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“…175 For this reason, there is a general consensus that all newborn infants should receive VK1 prophylaxis. 176,177 Although deficiency is rare in healthy adults, who typically get VK1 from green vegetables and VK2 from bacteria in their intestines, low levels of VK have been linked to several age-related diseases such as osteoporosis and bone fractures, 178 coronary heart disease, 179 neurodegenerative diseases, 180 and cancer, 181 COVID-19, 182 as well as metabolic disorders, mainly type 2 diabetes and obesity. 183 However, the precise ways in which VK may protect against these conditions are not yet fully understood and warrants further study.…”

Section: Reduced Vkh2mentioning

confidence: 99%

Endogenous chemicals guard health through inhibiting ferroptotic cell death

Song,

Lei,

et al. 2023

BioFactors

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Ferroptosis is a new form of regulated cell death caused by iron‐dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine‐glutathione‐glutathione peroxidase 4 system (cyst(e)ine‐GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7‐dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.

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New insights into vitamin K biology with relevance to cancer

Cited by 29 publications

References 148 publications

Blood-based epigenome-wide analyses on the prevalence and incidence of nineteen common disease states

Blood-based epigenome-wide analyses on the prevalence and incidence of nineteen common disease states

PANC-1 Cell Line as an Experimental Model for Characterizing PIVKA-II Production, Distribution, and Molecular Mechanisms Leading to Protein Release in PDAC

Endogenous chemicals guard health through inhibiting ferroptotic cell death

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