Vitamin K2 supplementation blocks the beneficial effects of IFN-α-2b administered on the early stages of liver cancer development in rats

Vera, Marina C.; Lorenzetti, Florencia; Lucci, Alvaro; Comanzo, Carla G.; Ceballos, María Paula; Pisani, G; Álvarez, María Clara; Quiroga, Ariel D.; Carrillo, María C.

doi:10.1016/j.nut.2018.08.016

Cited by 11 publications

(9 citation statements)

References 61 publications

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“…Inositol was also found to inhibit the occurrence and development of colorectal cancer and liver metastasis in BALB/c mice (Fu et al, 2016). On the other hand, vitamin K2 could block the beneficial effect of IFN-α-2b administered during early development of rat liver cancer (Vera et al, 2019). Moreover, the liver could reduce liver injury by degrading tryptophan, controlling heme synthesis and bilirubin metabolism, and producing immunomodulatory and active metabolites (Badawy, 2017).…”

Section: Discussionmentioning

confidence: 99%

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease

Yang

Kang³

et al. 2022

Journal of Dairy Science

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Alcoholic liver disease (ALD) is a liver disease caused by long-term heavy drinking, which is characterized by increased inflammation and oxidative stress in the liver and gut dysbiosis. The purpose of this study was to investigate the protective effect of administering ordinary and probiotic-(containing the Bifidobacterium animalis ssp. lactis Probio-M8 strain; M8) fermented milk to rats. Several biochemical parameters and the fecal metagenomes were monitored before (d 0) and after (d 42) the intervention. Our results confirmed that alcohol could cause significant changes in the liver levels of the proinflammatory cytokine IL-1β, antioxidation indicators, and liver function-related indicators; meanwhile, the gut bacterial and viral microbiota were disrupted with significant reduction in microbial diversity and richness. Feeding the rats with Probio-M8-fermented milk effectively maintained the gut microbiota stability, reduced liver inflammation and oxidative stress, and mitigated liver damages in ALD. Moreover, the Probio-M8-fermented milk reversed alcohol-induced dysbiosis by restoring the gut microbiota diversity, richness, and composition. Four predicted fecal metabolites (inositol, tryptophan, cortisol, and vitamin K2) increased after the intervention, which might help regulate liver metabolism and alleviate ALD-related symptoms. In short, our data supported that consuming Probio-M8-fermented milk effectively mitigated ALD. The protective effect against ALD could be related to changes in the gut microbiome after probiotic-fermented milk consumption. However, such observation and the causal relationship among probiotic milk consumption, changes in gut microbiome, and disease alleviation would still need to be further confirmed. Nevertheless, this study has shown in a rat model that consuming probiotic-fermented milk could protect against ALD.

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Section: Discussionmentioning

confidence: 99%

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease

Yang

Kang³

et al. 2022

Journal of Dairy Science

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“…To date, the outstanding anticancer functions of vitamin K as well as its analogs have been revealed in many studies (Dasari et al, 2017;Xv et al, 2018). Both vitamin K and its analogs were proved to exhibit their excellent abilities against the growth of multiple cancer cells through arresting cell cycle, regulating cell differentiation, and inducing autophagic or apoptotic cell death (Karasawa et al, 2013;Maniwa et al, 2015;Vera et al, 2019). However, the functions of PPM-18, as a novel analog of vitamin K, against human solid tumor were rarely reported.…”

Section: Discussionmentioning

confidence: 99%

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

Mei

Yang

et al. 2021

Front. Pharmacol.

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PPM-18, identified as a novel analog of vitamin K, has been reported to play a critical role in the suppression of seizures. However, the concerns that whether PPM-18, like vitamin K, exerts anticancer activity remain to be further investigated. Here, we found that PPM-18 remarkably suppressed the proliferation and induced apoptosis in bladder cancer cells. Furthermore, a significant autophagic effect of PPM-18 on bladder cancer cells was also demonstrated, which profoundly promoted apoptotic cell death. Mechanistically, PPM-18 activated AMP-activated protein kinase (AMPK), whereas it repressed PI3K/AKT and mTORC1 pathways in bladder cancer cells. Inhibition of AMPK markedly relieved PPM-18–induced autophagy and apoptosis, indicating that PPM-18 is able to induce autophagy and apoptosis in bladder cancer cells via AMPK activation. Moreover, reactive oxygen species (ROS) were notably accumulated in PPM-18–treated bladder cancer cells, and treatment with ROS scavengers not only eliminated ROS production but also abrogated AMPK activation, which eventually rescued bladder cancer cells from PPM-18–triggered autophagy and apoptotic cell death. In bladder cancer xenografts, the anticancer activities of PPM-18, including suppressing the growth of tumors and inducing autophagy and apoptosis in tumor cells, were also established. Collectively, this study was the first to demonstrate the anticancer effect of PPM-18 on bladder cancer cells in vitro and in vivo through eliciting autophagy and apoptosis via ROS and AMPK pathways, which might provide new insights into the potential utilization of PPM-18 for future bladder cancer treatment.

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“…This biological process is inhibited by warfarin (Figure 2). In addition to the well-known biological function of blood coagulation and bone metabolism, emerging studies support VK involved in multiple cellular and physiological processes such as oxidative stress (3,4), immune response and anti-inflammation (5,6), and cancer progression (7,8) and associated with protective and promoting roles in diverse organs or tissues, such as testis (9), brain (10)(11)(12)(13)(14), intestine (15)(16)(17), muscle (18,19), bone (20)(21)(22), liver (7,23), kidney (24,25), pancreas (26,27), fat tissues (28)(29)(30), and cardiovascular system (31-34) (Figure 3).…”

Section: Introductionmentioning

confidence: 99%

“…The present study focuses on the relationship between VK, intestinal health, and the mechanisms through which VK modulates intestinal microbes, exerts anti-inflammatory and antioxidant effects, and improves intestinal function. 9), brain (10)(11)(12)(13)(14), intestine (15)(16)(17), muscle (18,19), bone (20)(21)(22), liver (7,23), kidney (24,25), pancreas (26,27), fat tissues (28-30), and cardiovascular system (31)(32)(33)(34), and biological processes involved in anti-oxidation (3,4), immune response and antiinflammation (5,6), and cancer progression (7,8), and associated with protective and promoting roles in diverse organs or tissues throughout the human body are summarized above. The figure is in a non-editable format.…”

Section: Introductionmentioning

confidence: 99%

“… Functions of VK in multiple-organ systems, such as testis ( 9 ), brain ( 10 – 14 ), intestine ( 15 – 17 ), muscle ( 18 , 19 ), bone ( 20 – 22 ), liver ( 7 , 23 ), kidney ( 24 , 25 ), pancreas ( 26 , 27 ), fat tissues ( 28 – 30 ), and cardiovascular system ( 31 – 34 ), and biological processes involved in anti-oxidation ( 3 , 4 ), immune response and anti-inflammation ( 5 , 6 ), and cancer progression ( 7 , 8 ), and associated with protective and promoting roles in diverse organs or tissues throughout the human body are summarized above. The figure is in a non-editable format.…”

Section: Introductionmentioning

confidence: 99%

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Role of Vitamin K in Intestinal Health

Lai

Hori

et al. 2022

Front. Immunol.

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Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC) generally characterized by clinical symptoms, including malabsorption, intestinal dysfunction, injury, and microbiome imbalance, as well as certain secondary intestinal disease complications, continue to be serious public health problems worldwide. The role of vitamin K (VK) on intestinal health has drawn growing interest in recent years. In addition to its role in blood coagulation and bone health, several investigations continue to explore the role of VK as an emerging novel biological compound with the potential function of improving intestinal health. This study aims to present a thorough review on the bacterial sources, intestinal absorption, uptake of VK, and VK deficiency in patients with intestinal diseases, with emphasis on the effect of VK supplementation on immunity, anti-inflammation, intestinal microbes and its metabolites, antioxidation, and coagulation, and promoting epithelial development. Besides, VK-dependent proteins (VKDPs) are another crucial mechanism for VK to exert a gastroprotection role for their functions of anti-inflammation, immunomodulation, and anti-tumorigenesis. In summary, published studies preliminarily show that VK presents a beneficial effect on intestinal health and may be used as a therapeutic drug to prevent/treat intestinal diseases, but the specific mechanism of VK in intestinal health has yet to be elucidated.

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Vitamin K2 supplementation blocks the beneficial effects of IFN-α-2b administered on the early stages of liver cancer development in rats

Cited by 11 publications

References 61 publications

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

Role of Vitamin K in Intestinal Health

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