David Hoskin

David Hoskin
Dalhousie University | Dal · Department of Pathology

PhD

About

260
Publications
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7,575
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Publications

Publications (260)
Article
Full-text available
Breast cancer has historically been one of the leading causes of death for women worldwide. As of 2020, breast cancer was reported to have overtaken lung cancer as the most common type of cancer globally, representing an estimated 11.3% of all cancer diagnoses. A multidisciplinary approach is taken for the diagnosis and treatment of breast cancer t...
Article
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 act...
Article
Purpose: Iron is an essential trace element for the inflammatory response to infection. In this study, we determined the effect of the recently developed iron-binding polymer DIBI on the synthesis of inflammatory mediators by RAW 264.7 macrophages and bone marrow-derived macrophages in response to lipopolysaccharide (LPS) stimulation. Methods: Flow...
Article
Background/aim: Hepcidin is a cationic acute phase reactant synthesized by the liver. It has bactericidal properties and is a major regulator of iron homeostasis. Cationic antimicrobial peptides represent an innate antimicrobial defense system. We hypothesized that, like other cationic antimicrobial peptides, hepcidin is cytotoxic to cancer cells....
Article
Full-text available
Antimicrobial peptides (AMPs) found in the innate immune system of a wide range of organisms might prove useful to fight infections, due to the reported slower development of resistance to AMPs. Increasing the cationicity and keeping moderate hydrophobicity of the AMPs have been described to improve antimicrobial activity. We previously found a pep...
Article
Full-text available
Flavonoids are known to undergo phase II metabolism and produce metabolites with similar or stronger biological effects compared to the parent flavonoids. However, the limited cellular uptake and bioavailability restrict their clinical use. We synthesized phloridzin docosahexaenoate (PZ-DHA), a novel fatty acid ester of polyphenol, through an acyla...
Article
In this study, we determined the effect of low dose piperlongumine on the motility/invasive capacity and epithelial-to-mesenchymal transition (EMT) of MDA-MB-231 triple-negative breast cancer (TNBC) cells and the metastasis of 4T1 mouse mammary carcinoma cells. MTT assays measured the effect of piperlongumine on TNBC cell growth. Motility/invasiven...
Article
Full-text available
Anthocyanins are a group of dietary polyphenols, abundant mainly in fruits and their products. Dietary interventions of anthocyanins are being studied extensively related to the prevention of gastrointestinal (GI) cancer, among many other chronic disorders. This review summarizes the hereditary and non-hereditary characteristics of GI cancers, chem...
Article
Full-text available
In our previous study, we demonstrated that cyanidin-3-O-glucoside (C3G)-rich haskap (Lonicera caerulea L.) berry extracts can attenuate the carcinogen-induced DNA damage in normal lung epithelial cells in vitro. Here, the efficacy of lyophilized powder of whole haskap berry (C3G-HB) in lowering tobacco-specific nitrosamine, 4-(methylnitrosamino)-1...
Article
Full-text available
Direct-acting anticancer (DAA) peptides are cytolytic peptides that show promise as novel anticancer agents. DAA peptides bind to anionic molecules that are abundant on cancer cells relative to normal healthy cells, which results in preferential killing of cancer cells. Due to the mechanism by which DAA peptides kill cancer cells, it was thought th...
Article
Full-text available
Triple-negative breast cancer (TNBC) is an invasive subtype of breast cancer but paradoxically associated with increased tumor-infiltrating leukocytes. The molecular and cellular mechanisms underlying TNBC immunobiology are incompletely understood. Interleukin (IL)-17A is a pro-inflammatory cytokine that has both pro- and anti-tumor effects and fou...
Article
Background Myricetin is a polyphenolic compound that is cytostatic and/or cytotoxic for several cancer cell types; however, little is known about its effect on mammary carcinoma cells.Objective The objective of this study is to determine whether myricetin affects the growth of mammarycarcinoma cells.ResultsMyricetin inhibited the growth of 4T1 and...
Article
Diets rich in polyphenols are known to reduce cancer among high-risk populations. Haskap (Lonicera caerulea L.) berry has abundant phenolic acids and flavonoids, especially anthocyanins. Tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) present in cigarette smoke is a major lung carcinogenic factor. We analyzed the...
Article
Because of their highly reactive nature and potentially toxic characteristic, reactive oxygen species (ROS) have had a bad reputation for years. However, under certain conditions, ROS generation has shown positive outcomes. It is ROS imbalance that causes toxic effects. ROS play an important role in physiological processes such as cell signaling, s...
Article
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 aqueo...
Chapter
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 ex...
Article
Full-text available
Breast cancer is a leading cause of cancer-related death in women; however, chemotherapy of breast cancer is often hindered by dose-limiting toxicities, demonstrating the need for less toxic approaches to treatment. Since the rapid growth and metabolism of breast cancer cells results in an increased requirement for iron, withdrawal of bioavailable...
Article
Full-text available
Purpose: Gingerol homologs found in the rhizomes of ginger plants have the potential to benefit human health, including the prevention and treatment of cancer. This study evaluated the effect of 10-gingerol on ovarian cancer cell (HEY, OVCAR3, and SKOV-3) growth. Methods: Cell growth was measured by MTT assays, flow cytometry was used to assess ce...
Article
Full-text available
Many dietary flavonoids possess anti-cancer activities. Here, the effect of apple peel flavonoid fraction 4 (AF4) on the growth of triple-negative (MDA-MB-231, MDA-MB-468), estrogen receptor-positive (MCF-7), and HER2-positive (SKBR3) breast cancer cells was determined and compared with the effect of AF4 on normal mammary epithelial cells and derma...
Article
Triple-negative breast cancer (TNBC) tends to recur and metastasize following initial chemotherapy, which presents a treatment challenge. Here, we detail the anti-metastatic activity of phloridzin docosahexaenoate (PZ-DHA), synthesized from the natural polyphenol, phloridzin, and the ω-3 fatty acid, docosahexaenoic acid. Sub-cytotoxic PZ-DHA suppre...
Chapter
Anticancer peptides (ACPs) are cationic amphipathic peptides that bind to and kill cancer cells either by a direct- or indirect-acting mechanism. ACPs provide a novel treatment strategy, and selected ACPs are currently in phase I clinical trials to examine their safety and overall benefit in cancer patients. Increasing the selectivity of ACPs is im...
Article
Breast cancer is the most prevalent cancer diagnosis in women, with triple-negative and human epidermal growth factor 2 (HER2)-enriched advanced breast cancers having the poorest prognoses. The morbidity and mortality associated with advanced disease, as well as the emergence of multi-drug resistant variants, highlights the urgency to develop novel...
Article
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 etiolog...
Article
Full-text available
Transient Receptor Potential Melastatin-2 (TRPM2) ion channel is emerging as a great therapeutic target in many types of cancer, including gastric cancer – a major health threat of cancer related-death worldwide. Our previous study demonstrated the critical role of TRPM2 in gastric cancer cells bioenergetics and survival; however, its role in gastr...
Article
Full-text available
Thy-1 (CD90) is a glycosylphosphatidylinositol-anchored protein (GPI-AP) with signaling properties that is abundant on mouse T cells. Upon antibody-mediated crosslinking, Thy-1 provides a T cell receptor (TcR)-like signal that is sufficient to drive CD4+ T cell proliferation and differentiation into effector cells when costimulatory signals are pro...
Article
Widespread resistance to antimicrobial and cancer therapeutics is evolving in every country worldwide and has a direct impact on global health, agriculture and the economy. The specificity and selectivity of bioactive peptide natural products present a possible stopgap measure to address the ongoing deficit of new therapeutic compounds. PepSAVI-MS...
Article
Myricetin is a dietary phytochemical with anticancer activity; however, the effect of myricetin on breast cancer cells remains unclear. Here, we show that myricetin inhibited the growth of triple-negative breast cancer (TNBC) cells but was less inhibitory for normal cells. The effect of myricetin was comparable to epigallocatechin gallate and doxor...
Article
Full-text available
Proteoglycans are promising therapeutic targets in Multiple Sclerosis (MS), because they regulate many aspects of the immune response. This was studied using surfen, an agent that binds both heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs). Initial cell culture work on bone marrow derived macrophages (BMDMs) fou...
Chapter
Antimicrobial peptides (AMPs) are a class of small cationic peptides that are important for host defense. In a manner that is similar to AMP-mediated destruction of microbial pathogens, certain AMPs can physically associate with the anionic lipid membrane components of cancer cells, resulting in destabilization of the lipid membrane and subsequent...
Article
A number of polyphenolic compounds present in fruits and vegetables have the capacity to modulate immune responses; however, the impact of the common plant‐derived flavonoid myricetin on T lymphocyte function has not been investigated. We show that myricetin inhibited mouse T lymphocyte activation by bead‐immobilized anti‐CD3 and anti‐CD28 monoclon...
Article
Background: Iron catalyzes the generation of reactive oxygen species (ROS) as part of the innate antimicrobial defense. During sepsis, the dysregulated systemic inflammatory response to infection, iron homeostasis becomes disrupted, generating an excess of ROS causing damage to tissues. This can be potentially suppressed using iron chelators that...
Article
Antibody-mediated crosslinking of Thy-1 [also known as cluster of differentiation (CD)90], results in a T cell receptor (TcR)‑like signal; however, the impact of Thy‑1 stimulation in comparison to TcR stimulation on T cell activation and effector function has yet to be fully elucidated. In the present study, the outcome of Thy‑1‑ and TcR‑induced st...
Article
Full-text available
The reovirus FAST proteins are the smallest known viral fusogens (∼100-150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumour cells....
Conference Paper
In our previous studies, we showed the selective cytotoxicity, in vitro anti-proliferative and anti-metastatic activities of phloridzin docosahexaenoate (PZ-DHA). PZ-DHA combines phloridzin (PZ), a dihydrochalcone found in apple peels, and docosahexaenoic acid (DHA), an ω-3 fatty acid found in fish oil, through an acylation reaction. Significant su...
Article
Full-text available
The molecular mechanisms underlying aberrant activation of NF-κB and JNK in cancer remain incompletely understood. Here, we demonstrate that baseline IL-17 receptor (IL-17R) signaling is essential for controlling aberrant NF-κB and JNK activation, and restraining JNK-dependent homeostatic cellular proliferation. Using a shRNA knockdown approach, we...
Article
Full-text available
Vaccines that can rapidly induce strong and robust antibody-mediated immunity could improve protection from certain infectious diseases for which current vaccine formulations are inefficient. For indications such as anthrax and influenza, antibody production in vivo is a correlate of efficacy. Toll-like receptor (TLR) agonists are frequently studie...
Data
TLR3 knockout B cell stimulation. CD19+ B cells were purified from TLR3-/- (n = 5) or B6;129SF2/J wild type (n = 4) mice and stimulated with poly I:C (25 ug/mL), Pam3CSK4 (1 ug/mL) or the combination of both adjuvants for 24 hours in (A) T-cell-independent and (B) T-cell-dependent conditions. B cells were analysed by flow cytometry for expression o...
Data
Purity of B cells isolated from spleen. (A) Staining of C57BL/6 splenocyte starting populations with CD3-FITC (145-2C11), CD11c-PE (N418) and CD19-APC (1D3). (B) Staining of purified B cell populations for same markers. (C) Phenotypic analysis of purified B cells before culture staining with CD23-FITC (B3B4), B220-PE (RA3-6B2), CD5-APC (5373) and I...
Data
Representative histograms for isotype controls. Purified C57BL/6 CD19+ B cells were stimulated with poly I:C (25 ug/mL), Pam3CSK4 (1 ug/mL) or the combination of both adjuvants for 24 hours. B cells were then analysed by flow cytometry using isotype controls (A) Armenian Hamster IgG-FITC (eBio299Arm), (B) Rat IgG2a-PE (aBR2a), (C) Rat IgG1-APC (eBR...
Data
Dosing of poly I:C and PamCSK4 in vitro on B cell response. B cells were isolated from the spleens of naïve C57BL/6 mice (n = 3) and stimulated with various concentrations of poly I:C and Pam3SK4. Expression of CD40 (A), CD80 (B) and MHC class II (C) was determined by flow cytometry after 24 hour stimulation. Dashed line indicates level of unstimul...
Data
TLR2 knockout B cell stimulation. CD19+ B cells were purified from TLR2-/- (n = 4) or C57BL/6 wild type (n = 4) mice and stimulated with poly I:C (25 ug/mL), Pam3CSK4 (1 ug/mL) or the combination of both adjuvants for 24 hours in (A) T-cell-independent and (B) T-cell-dependent conditions. B cells were analysed by flow cytometry for expression of CD...
Data
Dose response to poly I:C and Pam3CSK4 combinations in vitro. B cells were isolated from the spleens of naïve C57BL/6 mice (n = 3) and stimulated with various concentrations of poly I:C and Pam3SK4 alone and in combination for 24 hours. Expression of CD80 (A), CD40 (B), MHC class II (C) was detected by flow cytometry. Secretion of IL-6 (D) was dete...
Data
Representative histograms for B cell surface marker expression. Purified C57BL/6 CD19+ B cells were stimulated with poly I:C (25 ug/mL), Pam3CSK4 (1 ug/mL) or the combination of both adjuvants for 24 hours. B cells were then analysed by flow cytometry for expression of CD86, CD80, CD25, MHC class II (IA/IE), CD69 and CD40. Results from multiple exp...
Data
Dosing of poly I:C and Pam3CSK4 in rPA vaccine. CD-1 mice were vaccinated with rPA antigen (2 ug) formulated with (A) poly I:C or (B) Pam3CSK4, at indicated doses, in DPX. Antigen-specific antibodies were detected in serum at 4 and 8 weeks post immunization. (TIF)
Article
Full-text available
The IL-17/IL-17R axis has controversial roles in cancer, which may be explained by tumor-specific results. Here, we describe a novel molecular mechanism underlying IL-17RC-controlled tumor-specific proliferation. Triggered by IL-17RC knockdown (KD), B16 melanoma and 4T1 carcinoma cells inversely altered homeostatic tumor proliferation and tumor gro...
Article
The ginger rhizome is rich in bioactive compounds, including [6]-gingerol, [8]-gingerol, and [10]-gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on [6]-gingerol. In this study, we compared [10]-gingerol with [8]-gingerol and [6]-gingerol in terms of their ability to inhibit the growth of human and...
Article
Proteoglycans as a double-edged sword in multiple sclerosis: Implications for future approaches to immunomodulatory therapy - Volume 44 Issue S1 - J Warford, AC Lamport, DW Hoskin, AS Easton
Article
Piperine has several well-documented anti-inflammatory properties; however, little is known regarding its effect on humoral immunity. In this study, we describe the immunosuppressive effect of piperine on B lymphocytes, which are integral to the humoral immune response. Mouse B cells were cultured in the absence or presence of non-cytotoxic concent...
Article
Anti-cancer peptides (ACPs) are small cationic and hydrophobic peptides that are more toxic to cancer cells than normal cells. ACPs kill cancer cells by causing irreparable membrane damage and cell lysis, or by inducing apoptosis. Direct-acting ACPs do not bind to a unique receptor, but are rather attracted to several different molecules on the sur...
Article
The recent increase in extensively drug resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs m...
Conference Paper
The molecular mechanisms underlying aberrant activation of NF-κB and JNK in cancer remain incompletely understood. Here, we demonstrate that baseline IL-17 receptor (IL-17R) signaling is essential for controlling aberrant NF-κB and JNK activation, and restraining JNK-dependent homeostatic cellular proliferation. Using a shRNA knockdown approach, we...
Article
Docosahexaenoic acid acylated-phloridzin (PZ-DHA), a novel polyphenol fatty acid ester derivative, was synthesized through a regioselective acylation reaction with the aim of increasing the bioactivity of phloridzin (PZ) and docosahexaenoic acid (DHA). In the current study, PZ-DHA’s cytotoxic activity was explored using in vitro and in vivo models...
Article
Background: Many plant-derived chemicals have been studied for their potential benefits in ailments including inflammation, cancer, neurodegeneration, and cardiovascular disease. The health benefits of phytochemicals are often attributed to the targeting of reactive oxygen species (ROS). However, it is not always clear whether these agents act dir...
Article
In this study, the antiproliferative and antimetastatic properties of phloridzin docosahexaenoate (PZ-DHA), a novel polyphenol fatty acid ester derivative, were explored using in vitro and in vivo models of mammary carcinoma. PZ-DHA combines phloridzin (PZ, a dihydrochalcone found in apple peels) with docosahexaenoic acid (DHA, an omega-3 fatty aci...
Article
Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN)-γ-induced PD-L1 upregulation by...
Article
Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also cont...
Article
Ovarian cancer is a leading cause of cancer-related death in women and the most lethal gynecological malignancy in the developed world. The morbidity and mortality of ovarian cancer underscore the need for novel treatment options. Artesunate (ART) is a well-tolerated anti-malarial drug that also has anti-cancer activity. In this study, we show that...
Article
Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatme...