Suppression of NNK Metabolism by Anthocyanin-Rich Haskap Berry Supplementation Through Modulation of P450 Enzymes.

Oral supplementation of anthocyanins-rich haskap () berry (HB) reduces 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis, cytotoxicity, DNA damage, and modulated inflammation in vitro and in vivo. The procarcinogen NNK is metabolically activated by cytochrome P450 (P450) enzymes, producing reactive metabolites that induce lung carcinogenesis. : Therefore, we hypothesized that the HB-modulated protective effect against NNK could be due to its ability to suppress P450 enzymes.

Phloridzin Docosahexaenoate, an Omega-3 Fatty Acid Ester of a Flavonoid Precursor, Inhibits Angiogenesis by Suppressing Endothelial Cell Proliferation, Migration, and Differentiation.

Angiogenesis is a normal physiological process that also contributes to diabetic retinopathy-related complications and facilitates tumor metastasis by promoting the hematogenic dissemination of malignant cells from solid tumors. Here, we investigated the in vitro, ex vivo, and in vivo anti-angiogenic activity of phloridzin docosahexaenoate (PZ-DHA), a novel ω-3 fatty acid ester of a flavonoid precursor. Human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC) treated with a sub-cytotoxic concentration of PZ-DHA to assess in vitro anti-angiogenic activity showed impaired tubule formation on a Matrigel matrix.

Phloridzin Docosahexaenoate Inhibits Spheroid Formation by Breast Cancer Stem Cells and Exhibits Cytotoxic Effects against Paclitaxel-Resistant Triple Negative Breast Cancer Cells.

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.

Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses.

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 (BMDMs) in response to lipopolysaccharide (LPS) stimulation.

Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.

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.

Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach.

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.

Regulation of macrophage-associated inflammatory responses by species-specific lactoferricin peptides.

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.

The Acute Phase Protein Hepcidin Is Cytotoxic to Human and Mouse Myeloma Cells.

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.

Dual Antimicrobial and Antiproliferative Activity of TcPaSK Peptide Derived from a Insect Defensin.

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 peptide derived from the insect defensin 3, exhibiting antrimicrobial activity against several human pathogens.

Metabolism and pharmacokinetics of a novel polyphenol fatty acid ester phloridzin docosahexaenoate in Balb/c female mice.

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 acylation reaction with the aim of increasing the cellular availability and stability of the parent biomolecules, phloridzin (PZ) and docosahexaenoic acid (DHA).

The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells.

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/invasiveness were determined by gap closure/transwell assays.

Chemopreventive Effect of Dietary Anthocyanins against Gastrointestinal Cancers: A Review of Recent Advances and Perspectives.

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, chemistry, and bioavailability of anthocyanins, and the most recent findings of anthocyanin in GI cancer prevention through modulating cellular signaling pathways.

MDA-MB-231 Breast Cancer Cells Resistant to Pleurocidin-Family Lytic Peptides Are Chemosensitive and Exhibit Reduced Tumor-Forming Capacity.

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 that resistance would be difficult to achieve.

Cyanidin-3--Glucoside-Rich Haskap Berry Administration Suppresses Carcinogen-Induced Lung Tumorigenesis in A/JCr Mice.

In our previous study, we demonstrated that cyanidin-3--glucoside (C3G)-rich haskap ( L.) berry extracts can attenuate the carcinogen-induced DNA damage in normal lung epithelial cells . Here, the efficacy of lyophilized powder of whole haskap berry (C3G-HB) in lowering tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)-induced lung tumorigenesis in A/JCr mice was investigated.

Myeloid-derived suppressor cell depletion therapy targets IL-17A-expressing mammary carcinomas.

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 found in 40-80% of TNBC samples.

Anthocyanin-rich haskap (Lonicera caerulea L.) berry extracts reduce nitrosamine-induced DNA damage in human normal lung epithelial cells in vitro.

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.

Instrumental role for reactive oxygen species in the inflammatory response.

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.

Delivery of Apoptosis-inducing Piperine to Triple-negative Breast Cancer Cells Co-polymeric Nanoparticles.

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.

Assessing the Impact of Phytochemicals on Immune Checkpoints: Implications for Cancer Immunotherapy.

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.

10-Gingerol Inhibits Ovarian Cancer Cell Growth by Inducing G2 Arrest.

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. Cell growth was measured by MTT assays, flow cytometry was used to assess cell proliferation, cytotoxicity and cell cycle progression, and western blotting was used to measure cyclin protein expression.

DIBI, a novel 3-hydroxypyridin-4-one chelator iron-binding polymer, inhibits breast cancer cell growth and functions as a chemosensitizer by promoting S-phase DNA damage.

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 iron using highly selective iron chelators has been suggested to represent a new approach to breast cancer treatment. Here we show that the recently developed iron-binding polymer DIBI inhibited the growth of five different breast cancer cell lines (SK-BR3, MDA-MB-468, MDA-MB-231, MCF-7, and T47D).

Apple Peel Flavonoid Fraction 4 Suppresses Breast Cancer Cell Growth by Cytostatic and Cytotoxic Mechanisms.

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 dermal fibroblasts. AF4 inhibited breast cancer cell growth in monolayer cultures, as well as the growth of MCF-7 spheroids, without substantially affecting the viability of non-malignant cells.

Examination of a day programme for eating disorders: impact on 3-month follow-up by psychiatric comorbidity.

Objective: The two aims of this preliminary investigation were to use a case series design to examine outcomes of a day programme (DP) for eating disorders and to investigate whether the presence of baseline psychiatric comorbidities moderated outcomes 3 months after discharge.

Method: Linear mixed modelling was used to investigate changes over time in the 91 participants who had commenced the DP by April 2019; 87 (96%) female, 61 (67%) with a DSM-5 diagnosis of anorexia nervosa.

Results: Six of our seven outcome variables (dietary restraint; concern over weight, eating and shape; clinical impairment; and psychological distress) showed moderate to large effect size improvements from baseline to follow-up.

Phloridzin docosahexaenoate, a novel fatty acid ester of a plant polyphenol, inhibits mammary carcinoma cell metastasis.

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 suppressed the migration of MDA-MB-231, SUM149, and 4T1 cells, as well as invasion by MDA-MB-231 and 4T1 cells.