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Article ; Online: Editorial: Immune Modulation by Flavonoids.

Hoskin, David W / Coombs, Melanie R Power

2022 Volume 13, Page(s) 899577

MeSH term(s)	Cytokines ; Flavonoids/pharmacology ; Flavonoids/therapeutic use ; Immunomodulating Agents/pharmacology ; Immunomodulating Agents/therapeutic use
Chemical Substances	Cytokines ; Flavonoids ; Immunomodulating Agents
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.899577
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Article ; Online: Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.

Amararathna, Madumani / Hoskin, David W / Rupasinghe, H P Vasantha

Oxidative medicine and cellular longevity

2022 Volume 2022, Page(s) 1422929

Abstract: Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues ... ...

Abstract	Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues and entrapment of anthocyanins increases their stability, bioavailability, and therapeutic efficacy. The objective of the present study was to develop a direct delivery system of anthocyanins into pulmonary tissues via encapsulated nanocarriers. A cyanidin-3-
MeSH term(s)	Animals ; Anthocyanins/metabolism ; Anthocyanins/pharmacology ; Anthocyanins/therapeutic use ; Carcinogens ; Chitosan ; DNA ; Glucosides ; Glucuronides ; Glutathione Peroxidase ; Humans ; Lung/metabolism ; Mice ; Nanoparticles ; Plant Extracts ; Superoxide Dismutase
Chemical Substances	Anthocyanins ; Carcinogens ; Glucosides ; Glucuronides ; Plant Extracts ; DNA (9007-49-2) ; Chitosan (9012-76-4) ; Glutathione Peroxidase (EC 1.11.1.9) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2022-09-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2022/1422929
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Article: Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses.

Ghassemi-Rad, Javad / Fernando, Wasundara / Holbein, Bruce E / Hoskin, David W

Advanced pharmaceutical bulletin

2022 Volume 13, Issue 2, Page(s) 368–377

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2022-01-02
Publishing country	Iran
Document type	Journal Article
ZDB-ID	3018440-X
ISSN	2251-7308 ; 2228-5881
ISSN (online)	2251-7308
ISSN	2228-5881
DOI	10.34172/apb.2023.040
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Article ; Online: Delivery of Apoptosis-inducing Piperine to Triple-negative Breast Cancer Cells

Rad, Javad Ghassemi / Hoskin, David W

Anticancer research

2020 Volume 40, Issue 2, Page(s) 689–694

Abstract: Background/aim: Piperine, a major alkaloid of the fruit of black pepper plants, selectively inhibits the growth of triple-negative breast cancer cells but its lipophilicity restricts possible clinical application. This study therefore determined the ... ...

Abstract	Background/aim: Piperine, a major alkaloid of the fruit of black pepper plants, selectively inhibits the growth of triple-negative breast cancer cells but its lipophilicity restricts possible clinical application. This study therefore determined the feasibility of encapsulating piperine in nanoparticles (NPs) to increase its solubility in an aqueous environment. Materials and methods: Piperine-loaded biodegradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic) acid copolymer-based NPs were produced by single emulsion solvent extraction and thin-film hydration. Growth and viability of triple-negative breast cancer (TNBC) cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin-V-FLUOS/propidium iodide staining, respectively. Results: Thin-film hydration was superior to single emulsion solvent extraction, yielding piperine-loaded NPs with an average size of 50 nm. Piperine-loaded NPs inhibited TNBC cell growth and induced apoptosis while sparing normal fibroblasts. Conclusion: It is feasible to deliver a cytotoxic concentration of piperine to TNBC cells via NPs with the potential for improved bioavailability and solubility in biological fluids.
MeSH term(s)	Alkaloids/administration & dosage ; Alkaloids/chemistry ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Agents, Phytogenic/chemistry ; Apoptosis/drug effects ; Benzodioxoles/administration & dosage ; Benzodioxoles/chemistry ; Cell Line, Tumor ; Emulsions/administration & dosage ; Emulsions/chemistry ; Female ; Humans ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Piperidines/administration & dosage ; Piperidines/chemistry ; Polyesters/administration & dosage ; Polyesters/chemistry ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/chemistry ; Polyunsaturated Alkamides/administration & dosage ; Polyunsaturated Alkamides/chemistry ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	Alkaloids ; Antineoplastic Agents, Phytogenic ; Benzodioxoles ; Emulsions ; Piperidines ; Polyesters ; Polyunsaturated Alkamides ; methoxypolyethyleneglycol-poly(lactic-co-glycolic acid) ; Polyethylene Glycols (3WJQ0SDW1A) ; piperine (U71XL721QK)
Language	English
Publishing date	2020-02-02
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.13998
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Article ; Online: Phloridzin Docosahexaenoate Inhibits Spheroid Formation by Breast Cancer Stem Cells and Exhibits Cytotoxic Effects against Paclitaxel-Resistant Triple Negative Breast Cancer Cells.

Fernando, Wasundara / Clark, Rikki F / Rupasinghe, H P Vasantha / Hoskin, David W / Coombs, Melanie R Power

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: The eradication of cancer stem cells (CSCs) is vital to successful cancer treatment and overall disease-free survival. CSCs are a sub-population of cells within a tumor that are defined by their capacity for continuous self-renewal and recapitulation of ... ...

Abstract	The eradication of cancer stem cells (CSCs) is vital to successful cancer treatment and overall disease-free survival. CSCs are a sub-population of cells within a tumor that are defined by their capacity for continuous self-renewal and recapitulation of new tumors, demonstrated in vitro through spheroid formation. Flavonoids are a group of phytochemicals with potent anti-oxidant and anti-cancer properties. This paper explores the impact of the flavonoid precursor phloridzin (PZ) linked to the ω-3 fatty acid docosahexaenoate (DHA) on the growth of MCF-7 and paclitaxel-resistant MDA-MB-231-TXL breast cancer cell lines. Spheroid formation assays, acid phosphatase assays, and Western blotting were performed using MCF-7 cells, and the cell viability assays, Annexin-V-488/propidium iodide (PI) staining, and 7-aminoactinomycin D (7-AAD) assays were performed using MDA-MB-231-TXL cells. PZ-DHA significantly reduced spheroid formation, as well as the metabolic activity of MCF-7 breast cancer cells in vitro. Treatment with PZ-DHA also suppressed the metabolic activity of MDA-MB-231-TXL cells and led to apoptosis. PZ-DHA did not have an observable effect on the expression of the drug efflux transporters ATP-binding cassette super-family G member 2 (ABCG2) and multidrug resistance-associated protein 1 (MRP1). PZ-DHA is a potential treatment avenue for chemo-resistant breast cancer and a possible novel CSC therapy. Future pre-clinical studies should explore PZ-DHA as a chemo-preventative agent.
MeSH term(s)	Humans ; Female ; Triple Negative Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Paclitaxel/therapeutic use ; Docosahexaenoic Acids/pharmacology ; Phlorhizin/pharmacology ; Cell Line, Tumor ; Antineoplastic Agents/therapeutic use ; ATP-Binding Cassette Transporters/metabolism ; Neoplastic Stem Cells/metabolism ; Cell Proliferation
Chemical Substances	Paclitaxel (P88XT4IS4D) ; Docosahexaenoic Acids (25167-62-8) ; Phlorhizin (CU9S17279X) ; Antineoplastic Agents ; ATP-Binding Cassette Transporters
Language	English
Publishing date	2023-09-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914577
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Article ; Online: Cyanidin-3-

Amararathna, Madumani / Hoskin, David W / Rupasinghe, H P Vasantha

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 17

Abstract: In our previous study, we demonstrated that cyanidin-3- ...

Abstract	In our previous study, we demonstrated that cyanidin-3-
MeSH term(s)	Animals ; Anthocyanins/chemistry ; Anthocyanins/pharmacology ; Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/pharmacology ; Carcinogenesis/chemically induced ; Carcinogenesis/metabolism ; Carcinogens/toxicity ; Fruit/chemistry ; Lonicera/chemistry ; Lung Neoplasms/chemically induced ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Magnetic Resonance Imaging ; Mice ; Plant Extracts/chemistry ; Positron-Emission Tomography
Chemical Substances	Anthocyanins ; Antineoplastic Agents, Phytogenic ; Carcinogens ; Plant Extracts ; cyanidin-3-O-beta-glucopyranoside
Language	English
Publishing date	2020-08-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25173823
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Article ; Online: Assessing the Impact of Phytochemicals on Immune Checkpoints: Implications for Cancer Immunotherapy.

Power Coombs, Melanie R / Hoskin, David W

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2111, Page(s) 161–173

Abstract: Phytochemicals are the basis for many anticancer drugs currently in clinical use, as well as a potential source of future cancer treatments. Some phytochemicals have been found to modify the expression of checkpoint inhibitors of the immune response, as ... ...

Abstract	Phytochemicals are the basis for many anticancer drugs currently in clinical use, as well as a potential source of future cancer treatments. Some phytochemicals have been found to modify the expression of checkpoint inhibitors of the immune response, as well as kill cancer cells. Cancer cells, in turn, may evade detection by the immune system by expressing molecules such as programmed death ligand 1 (PD-L1) that interacts with programmed cell death 1 (PD-1) on T cells to inhibit T cell activation and effector function. Phytochemicals have direct effects on cancer cells and/or T cells that may impact PD-L1/PD1 interactions, although this may vary depending on the phytochemical in question. Flow cytometric analysis of cancer cells stained with anti-PD-L1 antibodies following treatment with a given phytochemical enables the detection of any alteration in PD-L1 expression. The effect of the phytochemical on T cell function can be assessed using proliferation assays (e.g., tritiated thymidine incorporation, flow cytometric analysis of Oregon Green 488-stained cells) and enzyme-linked immunosorbent assay of interleukin-2 content in culture supernatants. Additional study is needed to better understand the impact of phytochemicals on cancer immunotherapy.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; B7-H1 Antigen/metabolism ; Cell Adhesion ; Cell Proliferation/drug effects ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunotherapy ; Jurkat Cells ; Lymphocyte Activation/drug effects ; Mice ; Neoplasms/drug therapy ; Neoplasms/immunology ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism
Chemical Substances	Antineoplastic Agents ; B7-H1 Antigen ; CD274 protein, human ; PDCD1 protein, human ; Phytochemicals ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0266-9_14
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Article: 10-Gingerol Inhibits Ovarian Cancer Cell Growth by Inducing G2 Arrest.

Rasmussen, Andrea / Murphy, Kaylee / Hoskin, David W

Advanced pharmaceutical bulletin

2019 Volume 9, Issue 4, Page(s) 685–689

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2019-10-24
Publishing country	Iran
Document type	Journal Article
ZDB-ID	3018440-X
ISSN	2251-7308 ; 2228-5881
ISSN (online)	2251-7308
ISSN	2228-5881
DOI	10.15171/apb.2019.080
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Article ; Online: Regulation of macrophage-associated inflammatory responses by species-specific lactoferricin peptides.

Malone, Alicia / Clark, Rikki F / Hoskin, David W / Power Coombs, Melanie R

Frontiers in bioscience (Landmark edition)

2022 Volume 27, Issue 2, Page(s) 43

Abstract: Background: Inflammation is the body's response to injury or infection and is important for healing and eliminating pathogens; however, prolonged inflammation is damaging and may lead to the development of chronic inflammatory disorders. Recently, there ...

Abstract	Background: Inflammation is the body's response to injury or infection and is important for healing and eliminating pathogens; however, prolonged inflammation is damaging and may lead to the development of chronic inflammatory disorders. Recently, there has been interest in exploiting antimicrobial peptides (AMPs) that exhibit immunoregulatory activities to treat inflammatory diseases. Methods: In this study, we investigated the immunomodulatory effects of lactoferrin-derived lactoferricin AMPs from three different species (bovine, mouse, and human) with subtle differences in their amino acid sequences that alter their antimicrobial action; to our knowledge, no other studies have compared their immunomodulatory effects. Macrophages, key players in the induction and propagation of inflammation, were used to investigate the effects of species-specific lactoferricin peptides on inflammatory processes. Results: Bovine lactoferricin was the only one of the three peptides studied that downregulated lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, in both human and mouse macrophages. Lactoferricin regulated inflammation through targeting LPS-activated nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Although the immunoregulatory role of lactoferricin during an inflammatory response Conclusions: The ability of lactoferricin, especially that of bovine origin, to downregulate macrophage-mediated inflammatory responses suggests potential for the development of this peptide as a novel immunotherapeutic agent in the treatment of chronic inflammatory conditions.
MeSH term(s)	Animals ; Cattle ; Cytokines/metabolism ; Humans ; Inflammation/metabolism ; Lactoferrin/adverse effects ; Lactoferrin/metabolism ; Lipopolysaccharides/pharmacology ; Macrophages/metabolism ; Mice ; NF-kappa B/metabolism ; Peptides/pharmacology
Chemical Substances	Cytokines ; Lipopolysaccharides ; NF-kappa B ; Peptides ; lactoferricin B (146897-68-9) ; Lactoferrin (EC 3.4.21.-)
Language	English
Publishing date	2022-02-28
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2702043
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Article ; Online: Dietary phytochemicals with anti-oxidant and pro-oxidant activities: A double-edged sword in relation to adjuvant chemotherapy and radiotherapy?

Fernando, Wasundara / Rupasinghe, H P Vasantha / Hoskin, David W

Cancer letters

2019 Volume 452, Page(s) 168–177

Abstract: Many advances have been made in the development and introduction of new anti-cancer drugs to the clinic. However, limited attention has been paid to improving the efficacy of currently available treatments through complementary phytochemical ... ...

Abstract	Many advances have been made in the development and introduction of new anti-cancer drugs to the clinic. However, limited attention has been paid to improving the efficacy of currently available treatments through complementary phytochemical interventions that affect cellular reactive oxygen species (ROS) levels, which are important for the etiology of certain cancers and the effectiveness of radiotherapy and some chemotherapy. In this regard, the maintenance of redox homeostasis may be influenced by the intake of anti-oxidant and pro-oxidant compounds from dietary sources. Interestingly, certain dietary phytochemicals exhibit both anti-oxidant and pro-oxidant activities, depending on their concentration and cellular microenvironment. There is evidence that concurrent administration of some dietary phytochemicals enhances the efficacy of certain cancer treatments by increasing intracellular ROS accumulation. Paradoxically, consumption of the same dietary phytochemicals under conditions that result in the scavenging of ROS might also negatively affect the outcome of ROS-dependent cancer treatments. This review discusses the potential impact of consuming dietary phytochemicals with anti-oxidant and/or pro-oxidant activities on the effectiveness of concurrent chemotherapy and/or radiotherapy in cancer patients.
MeSH term(s)	Antioxidants/pharmacology ; Drug Interactions/physiology ; Humans ; Neoplasms/pathology ; Neoplasms/therapy ; Oxidation-Reduction/drug effects ; Phytochemicals/pharmacology ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Tumor Microenvironment/physiology
Chemical Substances	Antioxidants ; Phytochemicals ; Reactive Oxygen Species
Language	English
Publishing date	2019-03-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2019.03.022
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