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Special Issue "Bioactivity of Inositol Phosphates"

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: 15 September 2020.

Special Issue Editor

Dr. Ivana Vucenik
Website
Guest Editor
University of Maryland School of Medicine, 100 Penn Street, Baltimore, Maryland 21201, USA
Interests: IP6, myo-inositol, and other cyclitols: methods and determination; biological role; health-promoting activities; cancer; insulin resistance; pathological calcification

Special Issue Information

Dear Colleagues, 

Inositol phosphates are a fascinating field of science. They belong to a huge and complex family of biomolecules, with important roles in cell regulation, signal transduction, energy transmission, and ion channels physiology, and serve as structural components of cell membranes. Inositol hexaphosphate (IP6 or InsP6 or phytic acid) and its parent compound myo-inositol are the most abundant, naturally occurring and widely distributed among plants and mammal’s tissues. Their discovery dates from the 1850s, when Hartig reported small round particles in various plant seeds, like potato starch grains (phytate). It was shown that these isolated particles were rich in phosphorous, calcium, and magnesium and were found only in plants, and the name “phytin” was created.
There are nine possible stereoisomers of inositol: cis-, epi-, allo-, myo-, muco-, neo-, (+)-chiro, (−)-chiro-, and scyllo-inositols, formed through the epimerization of its six hydroxyl groups. Although myo-inositol and IP6 have been extensively studied over the last three decades, the potential biological functions and possible medical applications of these other inositols and their phosphates have been recently considered.
IP6 and myo-inositol are active compounds of rice and other grains, with a broad spectrum of biological activities important in health and diseases. Their multiple health beneficial effects have been demonstrated in depression and anxiety disorders, neurodegenerative diseases, in inhibition of kidney stones formation and other pathological calcification, diabetes, metabolic syndrome, polycystic ovary syndrome, among many more. However, IP6 and myo-inositol have recently received much attention for their role in cancer prevention and treatment, shown in animals and humans. A consistent and reproducible anticancer activity has been demonstrated in different experimental models, targeting several key molecular targets, such as PI3K/Akt, MAPK, PKC, and NF-κB. Few clinical studies have indicated that IP6 alone or in combination with myo-inositol was able to enhance the anticancer effect of conventional therapy, control cancer metastases, and improve quality of life.
In this Special Issue a selection of research and review articles will cover a wide range of bioactivity of inositol phosphates from occurrence, chemistry, and methods for their determination in biological fluids, with numerous biological activities important in health and disease, with a focus on their most striking effect, the anticancer activity, that has been actively investigated during the last decades.

Dr. Ivana Vucenik
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Inositol hexaphosphate
  • Myo-inositol
  • Occurrence
  • Bioactivity
  • Depression and anxiety
  • Neurodegenerative diseases
  • Kidney stones
  • Diabetes
  • Metabolic syndrome
  • Polycystic ovary syndrome
  • Anticancer activity

Published Papers (4 papers)

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Research

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Open AccessArticle
Regulation of MicroRNA-155 and Its Related Genes Expression by Inositol Hexaphosphate in Colon Cancer Cells
Molecules 2019, 24(22), 4153; https://doi.org/10.3390/molecules24224153 - 16 Nov 2019
Abstract
Inositol hexaphosphate (IP6), a natural dietary component, has been found as an antitumor agent by stimulating apoptosis and inhibiting cancer cell proliferation, their migration, and metastasis in diverse cancers including colon cancer. However, molecular mechanisms of its action have not been well understood. [...] Read more.
Inositol hexaphosphate (IP6), a natural dietary component, has been found as an antitumor agent by stimulating apoptosis and inhibiting cancer cell proliferation, their migration, and metastasis in diverse cancers including colon cancer. However, molecular mechanisms of its action have not been well understood. In recent years, microRNAs (miRNAs) have been reported to play important roles in a broad range of biologic processes, such as cell growth, proliferation, apoptosis, or autophagy. These small noncoding molecules regulate post-transcriptional expression of targets genes via degradation of transcript or inhibition of protein synthesis. Aberrant expression and/or dysregulation of miRNAs have been characterized during tumor development and progression, thus, they are potential molecular targets for cancer prevention. The aim of this study was to investigate the effect of IP6 on the miRNAs expression profile in Caco-2 colon cancer cells. 84 miRNAs were analyzed in Caco-2 cells treated with 2.5 mM and 5 mM IP6 by the use of PCR (Polymerase Chain Reaction) array. The effect of 5 mM IP6 on selected potential miR-155 targets was determined by real-time (RT)-qPCR and ELISA (quantitative Polymerase Chain Reaction and Enzyme-Linked Immunosorbent Assay )method. The results indicated alteration in the specific 10 miRNA expression in human colon cancer cells following their treatment with 5 mM IP6. It down-regulated 8 miRNAs (miR-155, miR-210, miR-144, miR-194, miR-26b, miR-126, miR-302c, and miR-29a) and up-regulated 2 miRNAs (miR-223 and miR-196b). In silico analysis revealed that FOXO3a, HIF-1α, and ELK3 mRNAs are those of predicted targets of miR-155. IP6 at the concentration of 5 mM markedly induced FOXO3a and HIF-1a genes’ expression at both mRNA and protein level and decreased the amount of ELK3 mRNA as well as protein concentration in comparison to the control. In conclusion, the present study indicates that one of the mechanisms of antitumor potential of IP6 is down-regulation of the miR-155 expression in human colon cancer cells. Moreover, the expression of genes that are targeted by miRNA are also modulated by IP6. Full article
(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)
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Review

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Open AccessReview
Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals
Molecules 2020, 25(9), 2208; https://doi.org/10.3390/molecules25092208 - 08 May 2020
Abstract
Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many [...] Read more.
Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many key biological processes, including growth, vesicular remodeling, and energy homeostasis. PP-IPs function to regulate their target proteins through allosteric interactions or protein pyrophosphorylation. This review summarizes the current understanding of how PP-IPs control mammalian cellular signaling networks in physiology and disease. Full article
(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)
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Open AccessReview
Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases
Molecules 2020, 25(6), 1403; https://doi.org/10.3390/molecules25061403 - 19 Mar 2020
Cited by 1
Abstract
In mammals, a family of three inositol hexakisphosphate kinases (IP6Ks) synthesizes the inositol pyrophosphate 5-IP7 from IP6. Genetic deletion of Ip6k1 protects mice from high fat diet induced obesity, insulin resistance and fatty liver. IP6K1 generated 5-IP7 promotes insulin secretion from pancreatic β-cells, [...] Read more.
In mammals, a family of three inositol hexakisphosphate kinases (IP6Ks) synthesizes the inositol pyrophosphate 5-IP7 from IP6. Genetic deletion of Ip6k1 protects mice from high fat diet induced obesity, insulin resistance and fatty liver. IP6K1 generated 5-IP7 promotes insulin secretion from pancreatic β-cells, whereas it reduces insulin signaling in metabolic tissues by inhibiting the protein kinase Akt. Thus, IP6K1 promotes high fat diet induced hyperinsulinemia and insulin resistance in mice while its deletion has the opposite effects. IP6K1 also promotes fat accumulation in the adipose tissue by inhibiting the protein kinase AMPK mediated energy expenditure. Genetic deletion of Ip6k3 protects mice from age induced fat accumulation and insulin resistance. Accordingly, the pan IP6K inhibitor TNP [N2-(m-trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates obesity, insulin resistance and fatty liver in diet induced obese mice by improving Akt and AMPK mediated insulin sensitivity and energy expenditure. TNP also protects mice from bone loss, myocardial infarction and ischemia reperfusion injury. Thus, the IP6K pathway is a potential target in obesity and other metabolic diseases. Here, we summarize the studies that established IP6Ks as a potential target in metabolic diseases. Further studies will reveal whether inhibition of this pathway has similar pleiotropic benefits on metabolic health of humans. Full article
(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)
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Open AccessReview
Key Aspects of Myo-Inositol Hexaphosphate (Phytate) and Pathological Calcifications
Molecules 2019, 24(24), 4434; https://doi.org/10.3390/molecules24244434 - 04 Dec 2019
Cited by 1
Abstract
Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease [...] Read more.
Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine. Full article
(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)
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