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Article ; Online: A novel approach to overcome drug resistance in acute myeloid leukemia.

Mazewski, Candice / Platanias, Leonidas C

2023 Volume 108, Issue 11, Page(s) 2889–2890

MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Drug Resistance, Neoplasm/genetics
Language	English
Publishing date	2023-11-01
Publishing country	Italy
Document type	Editorial ; Comment
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283099
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Article: MNK Proteins as Therapeutic Targets in Leukemia.

Mazewski, Candice / Platanias, Leonidas C

OncoTargets and therapy

2023 Volume 16, Page(s) 283–295

Abstract: In leukemia, resistance to therapy is a major concern for survival. MAPK-interacting kinases (MNKs) have been identified as important activators of oncogenic-related signaling and may be mediators of resistance. Recent studies in leukemia models, ... ...

Abstract	In leukemia, resistance to therapy is a major concern for survival. MAPK-interacting kinases (MNKs) have been identified as important activators of oncogenic-related signaling and may be mediators of resistance. Recent studies in leukemia models, especially acute myeloid leukemia (AML), have focused on targeting MNKs together with other inhibitors or treating chemotherapy-resistant cells with MNK inhibitors. The preclinical demonstrations of the efficacy of MNK inhibitors in these combination formats would suggest a promising potential for use in clinical trials. Optimizing MNK inhibitors and testing in leukemia models is actively being pursued and may have important implications for the future. These studies are furthering the understanding of the mechanisms of MNKs in cancer which could translate to clinical studies.
Language	English
Publishing date	2023-04-21
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S370874
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways.

Mazewski, Candice / Perez, Ricardo E / Fish, Eleanor N / Platanias, Leonidas C

Frontiers in immunology

2020 Volume 11, Page(s) 606456

Abstract: For several decades there has been accumulating evidence implicating type I interferons (IFNs) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type I IFN proteins have been successfully employed to treat ...

Abstract	For several decades there has been accumulating evidence implicating type I interferons (IFNs) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type I IFN proteins have been successfully employed to treat a diverse group of diseases with significant and positive outcomes. The biological activities of type I IFNs are consequences of signaling events occurring in the cytoplasm and nucleus of cells. Biochemical events involving JAK/STAT proteins that control transcriptional activation of IFN-stimulated genes (ISGs) were the first to be identified and are referred to as "canonical" signaling. Subsequent identification of JAK/STAT-independent signaling pathways, critical for ISG transcription and/or mRNA translation, are denoted as "non-canonical" or "non-classical" pathways. In this review, we summarize these signaling cascades and discuss recent developments in the field, specifically as they relate to the biological and clinical implications of engagement of both canonical and non-canonical pathways.
MeSH term(s)	Animals ; Humans ; Interferon Type I/immunology ; Janus Kinases/immunology ; Protein Biosynthesis/immunology ; STAT Transcription Factors/immunology ; Signal Transduction/immunology ; Transcription, Genetic/immunology
Chemical Substances	Interferon Type I ; STAT Transcription Factors ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2020-11-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.606456
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro, in silico, and biochemical assays

Mazewski, Candice / Katie Liang / Elvira Gonzalez de Mejia

Food chemistry. 2018 Mar. 01, v. 242

2018

Abstract: The objective was to compare the anti-proliferative effect of anthocyanin-rich plant extracts on human colon cancer cells and determine their mechanism of action. Eleven extracts were tested: red (RG) and purple grape, purple sweet potato, purple carrot, ...

Abstract	The objective was to compare the anti-proliferative effect of anthocyanin-rich plant extracts on human colon cancer cells and determine their mechanism of action. Eleven extracts were tested: red (RG) and purple grape, purple sweet potato, purple carrot, black and purple bean, black lentil (BL), black peanut, sorghum (SH), black rice, and blue wheat. HCT-116 and HT-29 inhibition correlated with total phenolics (r=0.87 and 0.77, respectively), delphinidin-3-O-glucoside concentration with HT-29 inhibition (r=0.69). The concentration inhibition fifty (IC50) for BL, SH, RG on HT-29 and HCT-116 cell proliferation ranged 0.9â2.0mg/mL. Extracts decreased expression of anti-apoptotic proteins (survivin, cIAP-2, XIAP), induced apoptosis, and arrested cells in G1. Anthocyanins exhibited tyrosine kinase inhibitory potential in silico and biochemically; cyanidin-3-O-glucoside had one of the highest binding affinities with all kinases, especially ABL1 (â8.5kcal/mol). Cyanidin-3-O-glucoside and delphinidin-3-O-glucoside inhibited EGFR (IC50=0.10 and 2.37ÂµM, respectively). Cyanidin-3-O-glucoside was the most potent anthocyanin on kinase inhibition.
Keywords	anthocyanins ; apoptosis ; beans ; binding capacity ; black rice ; carrots ; cell proliferation ; chemical composition ; colorectal neoplasms ; grapes ; humans ; inhibitory concentration 50 ; lentils ; mechanism of action ; neoplasm cells ; peanuts ; phenolic compounds ; phosphotransferases (kinases) ; plant extracts ; pro-apoptotic proteins ; sweet potatoes ; tyrosine ; wheat
Language	English
Dates of publication	2018-0301
Size	p. 378-388.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2017.09.086
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Anthocyanins, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, inhibit immune checkpoints in human colorectal cancer cells in vitro and in silico.

Mazewski, Candice / Kim, Morgan Sanha / Gonzalez de Mejia, Elvira

Scientific reports

2019 Volume 9, Issue 1, Page(s) 11560

Abstract: The objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) and its ... ...

Abstract	The objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) and its metabolites, delphinidin (DC) and gallic acid (GA), were tested alone or in combination, on HCT-116 and HT-29 human colorectal cancer cells (100-600 µg/mL). HCT-116 and HT-29 50% inhibition concentrations (µg/mL) were 396 ± 23 and 329 ± 17 for D3G; 242 ± 16 and >600 for DC; and 154 ± 5 and 81 ± 5 for GA, respectively. Using molecular docking, cyanidin-3-O-glucoside (C3G) showed the highest potential to inhibit immune checkpoints: programmed cell death protein-1 (PD-1) (-6.8 kcal/mol) and programmed death-ligand-1 (PD-L1) (-9.6 kcal/mol). C3G, D3G, DC, GA, and D3G-rich extracts decreased PD-L1 protein expression in HCT-116 cells. C3G decreased PD-L1 fluorescence intensity by 39%. ANC decreased PD-1 expression in peripheral blood mononuclear cells in monoculture by 41% and 55%, and co-culture with HCT-116 and HT-29 cells by 39% and 26% (C3G) and 50% and 51% (D3G), respectively. D3G and C3G, abundant in plant foods, showed potential for binding with and inhibiting immune checkpoints, PD-1 and PD-L1, which can activate immune response in the tumor microenvironment and induce cancer cell death.
MeSH term(s)	Adjuvants, Immunologic/chemistry ; Adjuvants, Immunologic/pharmacology ; Anthocyanins/chemistry ; Anthocyanins/pharmacology ; Antineoplastic Agents, Immunological/chemistry ; Antineoplastic Agents, Immunological/pharmacology ; Cell Survival/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/immunology ; Glucosides/chemistry ; Glucosides/pharmacology ; HCT116 Cells ; HT29 Cells ; Humans ; Tumor Microenvironment/drug effects
Chemical Substances	Adjuvants, Immunologic ; Anthocyanins ; Antineoplastic Agents, Immunological ; Glucosides ; cyanidin-3-O-beta-glucopyranoside ; delphinidin (EM6MD4AEHE)
Language	English
Publishing date	2019-08-09
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47903-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Reduction of colitis-associated colon carcinogenesis by a black lentil water extract through inhibition of inflammatory and immunomodulatory cytokines

Mazewski, Candice / Luna-Vital, Diego / Berhow, Mark / de Mejia, Elvira Gonzalez

Carcinogenesis. 2020 June, v. 41, no. 6

2020

Abstract: The objective was to compare the impact of black lentil (BL) water and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extracts on tumor development, inflammation and immune response in an azoxymethane (AOM)/dextran ... ...

Abstract	The objective was to compare the impact of black lentil (BL) water and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extracts on tumor development, inflammation and immune response in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), AOM/DSS control (n = 14), AOM/DSS + BL (600 mg/kg body wt, n = 12) and AOM/DSS + D3G (41 mg/kg body wt, equivalent to D3G concentration in BL, n = 12). Mice were given treatments for 11 weeks using a voluntary jelly administration. AOM/DSS + BL presented a lower (P < 0.05) disease activity index, throughout and at the end (2.4) compared with AOM/DSS (6.3). AOM/DSS + BL mice had an average of 7.8 neoplasms versus 12.8 for the AOM/DSS (P < 0.05). Proinflammatory cytokines were downregulated in the colon mucosa: interleukin (IL)-1β (-77.5%, -70.7%) and IL-6 (-44.4%, -44.9%) by AOM/DSS + BL and AOM/DSS + D3G, respectively, compared with AOM/DSS. IL-6 protein expression was decreased by BL in plasma (-72.6%) and gene expression in colon polyps (fold change: -4.0) compared with AOM/DSS. AOM/DSS + D3G non-polyp tissue gene expression clustered with the healthy control tissue with only four genes modified (secreted phosphoprotein 1 and CXC motif chemokine ligands 2, 5 and 10). AOM/DSS + BL downregulated programmed death-ligand 1 protein expression in colon tissue (-54.7%) and gene expression by 2.8-fold compared with the AOM/DSS control. In fecal samples, gallic and protocatechuic acids and epicatechin were found, and concentration of most amino acids was lower and unsaturated fatty acids were higher for AOM/DSS + BL and AOM/DSS + D3G. BL and D3G-rich extracts showed anti-inflammatory and proimmune response effects while BL additionally prevented growth of neoplasia.
Keywords	azoxymethane ; carcinogenesis ; chemokines ; colon ; delphinidin ; epicatechin ; gene expression ; immune response ; inflammation ; interleukin-6 ; lentils ; ligands ; models ; mucosa ; neoplasms ; phosphoproteins ; protein synthesis ; sodium sulfate
Language	English
Dates of publication	2020-06
Size	p. 790-803.
Publishing place	Oxford University Press (OUP)
Document type	Article
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgaa008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro, in silico, and biochemical assays.

Mazewski, Candice / Liang, Katie / Gonzalez de Mejia, Elvira

Food chemistry

2017 Volume 242, Page(s) 378–388

Abstract	The objective was to compare the anti-proliferative effect of anthocyanin-rich plant extracts on human colon cancer cells and determine their mechanism of action. Eleven extracts were tested: red (RG) and purple grape, purple sweet potato, purple carrot, black and purple bean, black lentil (BL), black peanut, sorghum (SH), black rice, and blue wheat. HCT-116 and HT-29 inhibition correlated with total phenolics (r=0.87 and 0.77, respectively), delphinidin-3-O-glucoside concentration with HT-29 inhibition (r=0.69). The concentration inhibition fifty (IC
MeSH term(s)	Anthocyanins/pharmacology ; Cell Proliferation/drug effects ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/physiopathology ; Glucosides/pharmacology ; HCT116 Cells ; HT29 Cells ; Humans ; Phenols/pharmacology ; Plant Extracts/chemistry ; Plant Extracts/pharmacology
Chemical Substances	Anthocyanins ; Glucosides ; Phenols ; Plant Extracts ; cyanidin-3-O-beta-glucopyranoside ; delphinidin 3-O-glucopyranoside (474A9U89JS)
Language	English
Publishing date	2017-09-18
Publishing country	England
Document type	Journal Article
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2017.09.086
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reduction of colitis-associated colon carcinogenesis by a black lentil water extract through inhibition of inflammatory and immunomodulatory cytokines.

Mazewski, Candice / Luna-Vital, Diego / Berhow, Mark / Gonzalez de Mejia, Elvira

Carcinogenesis

2020 Volume 41, Issue 6, Page(s) 790–803

Abstract	The objective was to compare the impact of black lentil (BL) water and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extracts on tumor development, inflammation and immune response in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), AOM/DSS control (n = 14), AOM/DSS + BL (600 mg/kg body wt, n = 12) and AOM/DSS + D3G (41 mg/kg body wt, equivalent to D3G concentration in BL, n = 12). Mice were given treatments for 11 weeks using a voluntary jelly administration. AOM/DSS + BL presented a lower (P < 0.05) disease activity index, throughout and at the end (2.4) compared with AOM/DSS (6.3). AOM/DSS + BL mice had an average of 7.8 neoplasms versus 12.8 for the AOM/DSS (P < 0.05). Proinflammatory cytokines were downregulated in the colon mucosa: interleukin (IL)-1β (-77.5%, -70.7%) and IL-6 (-44.4%, -44.9%) by AOM/DSS + BL and AOM/DSS + D3G, respectively, compared with AOM/DSS. IL-6 protein expression was decreased by BL in plasma (-72.6%) and gene expression in colon polyps (fold change: -4.0) compared with AOM/DSS. AOM/DSS + D3G non-polyp tissue gene expression clustered with the healthy control tissue with only four genes modified (secreted phosphoprotein 1 and CXC motif chemokine ligands 2, 5 and 10). AOM/DSS + BL downregulated programmed death-ligand 1 protein expression in colon tissue (-54.7%) and gene expression by 2.8-fold compared with the AOM/DSS control. In fecal samples, gallic and protocatechuic acids and epicatechin were found, and concentration of most amino acids was lower and unsaturated fatty acids were higher for AOM/DSS + BL and AOM/DSS + D3G. BL and D3G-rich extracts showed anti-inflammatory and proimmune response effects while BL additionally prevented growth of neoplasia.
MeSH term(s)	Animals ; Azoxymethane/toxicity ; Carcinogenesis ; Carcinogens/toxicity ; Colitis/chemically induced ; Colitis/complications ; Colitis/pathology ; Colonic Neoplasms/etiology ; Colonic Neoplasms/pathology ; Colonic Neoplasms/prevention & control ; Cytokines/pharmacology ; Dextran Sulfate/toxicity ; Fabaceae/chemistry ; Gene Expression Profiling ; Inflammation/etiology ; Inflammation/pathology ; Inflammation/prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Plant Extracts/pharmacology ; Water/chemistry
Chemical Substances	Carcinogens ; Cytokines ; Plant Extracts ; Water (059QF0KO0R) ; Dextran Sulfate (9042-14-2) ; Azoxymethane (MO0N1J0SEN)
Language	English
Publishing date	2020-01-31
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgaa008
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Article: Inhibitory potential of anthocyanin-rich purple and red corn extracts on human colorectal cancer cell proliferation in vitro

Mazewski, Candice / Elvira Gonzalez de Mejia / Katie Liang

Journal of functional foods. 2017 July, v. 34

2017

Abstract: Anthocyanin-rich foods have shown potential health benefits. The objective was to evaluate the anti-proliferative effect of anthocyanin-rich purple and red corn on HCT-116 and HT-29 human colorectal cancer cells. IC50 values ranged from 1.1 to 6.3mg/mL, ... ...

Abstract	Anthocyanin-rich foods have shown potential health benefits. The objective was to evaluate the anti-proliferative effect of anthocyanin-rich purple and red corn on HCT-116 and HT-29 human colorectal cancer cells. IC50 values ranged from 1.1 to 6.3mg/mL, suggesting the corn extracts exhibited anti-proliferative effects on colon cancer cells; the red corn had the highest potential. All extracts increased apoptotic cells and impacted markers of apoptosis (BAX, Bcl-2, cytochrome c, TRAILR2/D5). Angiogenesis markers were also affected; a decreased expression of VEGF resulted with all corn extracts. Red corn significantly reduced other important markers of angiogenesis like Tie-2. Free binding energy of anthocyanins to tyrosine kinases was estimated at −7.86 and −7.76kcal/mol for cyanidin-3-glucoside with a non-receptor tyrosine kinase and peonidin with a receptor tyrosine kinase, respectively. The results indicate that anthocyanin-rich purple and red corn can potentially inhibit human colon cancer cell proliferation through promoting apoptosis and suppressing angiogenesis.
Keywords	angiogenesis ; anthocyanins ; apoptosis ; cell proliferation ; colorectal neoplasms ; corn ; cytochrome c ; energy ; foods ; human cell lines ; humans ; inhibitory concentration 50 ; neoplasm cells ; receptor protein-tyrosine kinase ; tyrosine ; vascular endothelial growth factors
Language	English
Dates of publication	2017-07
Size	p. 254-265.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2511964-3
ISSN	1756-4646
ISSN	1756-4646
DOI	10.1016/j.jff.2017.04.038
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Anthocyanins, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, inhibit immune checkpoints in human colorectal cancer cells in vitro and in silico

Candice Mazewski / Morgan Sanha Kim / Elvira Gonzalez de Mejia

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 15

Abstract: Abstract The objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) ...

Abstract	Abstract The objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) and its metabolites, delphinidin (DC) and gallic acid (GA), were tested alone or in combination, on HCT-116 and HT-29 human colorectal cancer cells (100–600 µg/mL). HCT-116 and HT-29 50% inhibition concentrations (µg/mL) were 396 ± 23 and 329 ± 17 for D3G; 242 ± 16 and >600 for DC; and 154 ± 5 and 81 ± 5 for GA, respectively. Using molecular docking, cyanidin-3-O-glucoside (C3G) showed the highest potential to inhibit immune checkpoints: programmed cell death protein-1 (PD-1) (−6.8 kcal/mol) and programmed death-ligand-1 (PD-L1) (−9.6 kcal/mol). C3G, D3G, DC, GA, and D3G-rich extracts decreased PD-L1 protein expression in HCT-116 cells. C3G decreased PD-L1 fluorescence intensity by 39%. ANC decreased PD-1 expression in peripheral blood mononuclear cells in monoculture by 41% and 55%, and co-culture with HCT-116 and HT-29 cells by 39% and 26% (C3G) and 50% and 51% (D3G), respectively. D3G and C3G, abundant in plant foods, showed potential for binding with and inhibiting immune checkpoints, PD-1 and PD-L1, which can activate immune response in the tumor microenvironment and induce cancer cell death.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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