Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation

Zhang, Hao; Ozaki, Iwata; Hamajima, Hiroshi; Iwane, Shinji; Takahashi, Hirokazu; Kawaguchi, Yasunori; Eguchi, Yuichiro; Yamamoto, Kyosuke; Mizuta, Toshihiko

doi:10.3892/or_00001056

Cited by 12 publications

(2 citation statements)

References 22 publications

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“…A combination of VK2 with other therapeutic or investigational agents has been shown. Using in vitro models, enhancement of the inhibition of HCC cell proliferation with the combination of 5-fluorouracil and VK2 was shown [ 162 ], while cell-cycle arrest and apoptosis was demonstrated with sorafenib/VK2 [ 163 ]. A recent study in a clinic involving 44 HCC patients further demonstrated the efficacy and safety of VK2 and sorafenib combination treatment, where significantly higher objective response rates and extended median time of progression-free survival were observed in the combination treatment group compared to that of sorafenib alone [ 164 ].…”

Section: Potential Therapeutic Benefitsmentioning

confidence: 99%

Vitamin K2 in Health and Disease: A Clinical Perspective

Zhang,

O’Connor,

Sheridan

et al. 2024

Foods

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Vitamins are essential organic compounds that vary widely in chemical structure and are vital in small quantities for numerous biochemical and biological functions. They are critical for metabolism, growth, development and maintaining overall health. Vitamins are categorised into two groups: hydrophilic and lipophilic. Vitamin K (VK), a lipophilic vitamin, occurs naturally in two primary forms: phylloquinone (VK1), found in green leafy vegetables and algae, and Menaquinones (VK2), present in certain fermented and animal foods and widely formulated in VK supplements. This review explores the possible factors contributing to VK deficiency, including dietary influences, and discusses the pharmacological and therapeutic potential of supplementary VK2, examining recent global clinical studies on its role in treating diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, diabetes, neurodegenerative disorders and cancers. The analysis includes a review of published articles from multiple databases, including Scopus, PubMed, Google Scholar, ISI Web of Science and CNKI, focusing on human studies. The findings indicate that VK2 is a versatile vitamin essential for human health and that a broadly positive correlation exists between VK2 supplementation and improved health outcomes. However, clinical data are somewhat inconsistent, highlighting the need for further detailed research into VK2′s metabolic processes, biomarker validation, dose–response relationships, bioavailability and safety. Establishing a Recommended Daily Intake for VK2 could significantly enhance global health.

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Section: Potential Therapeutic Benefitsmentioning

confidence: 99%

Vitamin K2 in Health and Disease: A Clinical Perspective

Zhang,

O’Connor,

Sheridan

et al. 2024

Foods

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“…Vitamin K 2 could suppress the expression of MMPs that possess NF-κB binding motifs in their promoter regions [21]. Additionally, vitamin K 2 has been found to enhance the inhibitory effect of 5-fluorouracil on the growth of hepatocellular carcinoma (HCC) cells by inhibiting the activation of NF-κB [339]. Therefore, the vitamin K2-mediated inhibition of NF-κB is thought to be involved in suppressing multiple MMPs.…”

Section: Vitamin K In Human Disease Treatment and Mmp Regulationmentioning

confidence: 99%

Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity

Vo,

Nguyen,

Kim

et al. 2023

IJMS

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Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases’ (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.

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Evaluation of the antitumor effects of vitamin K2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate

Shi

Zhou

Kang

et al. 2017

Drug Deliv. and Transl. Res.

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Numerous studies have recently shown that vitamin K (VK) has antitumor effects in a variety of tumor cells, but there are few reports demonstrating antitumor effects of VK in vivo. The antitumor effects of VK in nanoemulsions are currently not known. Therefore, we sought to characterize the antitumor potential of VK nanoemulsions in S180 tumor cells in the present study. Furthermore, a ligand conjugate sialic acid-cholesterol, with enhanced affinity towards the membrane receptors overexpressed in tumors, was anchored on the surface of the nanoemulsions to increase VK distribution to the tumor tissue. VK was encapsulated in oil-in-water nanoemulsions, and the physical and chemical stability of the nanoemulsions were characterized during storage at 25 °C. At 25 °C, all nanoemulsions remained physically and chemically stable with little change in particle size. An in vivo study using syngeneic mice with subcutaneously established S180 tumors demonstrated that intravenous or intragastric administration of VK nanoemulsions significantly suppressed the tumor growth. The VK nanoemulsions modified with sialic acid-cholesterol conjugate showed higher tumor growth suppression than the VK nanoemulsions, while neither of them exhibited signs of drug toxicity. In summary, VK exerted effective antitumor effects in vivo, and VK nanoemulsions modified with sialic acid-cholesterol conjugate enhanced the antitumor activity, suggesting that these VK may be promising agents for the prevention or treatment of tumor in patients.

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Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation

Cited by 12 publications

References 22 publications

Vitamin K2 in Health and Disease: A Clinical Perspective

Vitamin K2 in Health and Disease: A Clinical Perspective

Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity

Evaluation of the antitumor effects of vitamin K2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate

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