Solasodine Downregulates ABCB1 Overexpression in Multidrug Resistant Cancer Cells Via Inhibiting Nrf2/Keap1 Signaling Pathway

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

ABSTRACT Multidrug‐resistant (MDR) cancer cells maintain redox homeostasis to eliminate oxidative stress‐mediated cell death. This study explores the effects of solasodine on regulating P‐glycoprotein (P‐gp) expression through Nrf2/Keap1 signaling pathway and stress‐induced sensitization drug‐resistant chemotherapeutics. Initially, stress indicators such as intracellular ROS generation, levels 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) gamma‐H2AX (γ‐H2AX) in KBChR‐8‐5 were measured. Additionally, protein Nuclear factor erythroid 2‐related 2 (Nrf‐2), Kelch‐like ECH‐associated 1 (Keap1), ATP Binding Cassette Subfamily B Member (ABCB1)/P‐gp measured at various concentrations (1, 5, & 10 µM) immunofluorescence western blot analysis. The antioxidant activities assessed using established protocols. In this investigation, treatment with doxorubicin combination showed a notable increase generation cells. Furthermore, led enhanced nuclear condensation, elevated 8‐OHdG, increased γ‐H2AX foci formation Solasodine effectively inhibited translocation Nrf2 activation ABCB1 gene, consequently preventing overexpression P‐gp therapy lipid peroxidation while simultaneously reducing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), (GSH). These results demonstrated that disrupts balance, overcomes drug resistance by downregulating via MDR

Language: Английский

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Anti-Inflammatory and Anticancer Effects of Kaurenoic Acid in Overcoming Radioresistance in Breast Cancer Radiotherapy

Nutrients, Journal Year: 2024, Volume and Issue: 16(24), P. 4320 - 4320

Published: Dec. 14, 2024

Background/Objectives: Peroxisome proliferator–activated receptor γ (PPARγ) plays a key role in mediating anti-inflammatory and anticancer effects the tumor microenvironment. Kaurenoic acid (KA), diterpene compound isolated from Sphagneticola trilobata (L.) Pruski, has been demonstrated to exert anti-inflammatory, anticancer, antihuman immunodeficiency virus effects. Methods: In this study, we identified KA as novel activator of PPARγ with potent antitumor both vitro vivo. Given potential regulators overcoming radioresistance chemoresistance cancer therapies, hypothesized that may enhance efficacy breast radiotherapy. Results: lipopolysaccharide (LPS)-induced mouse inflammation model, treatment reduced levels pro-inflammatory cytokines, including COX-2, IL-6, IL-1β, TNFα. xenograft mode cancer, inhibited growth. Specifically, enhanced caspase-3 activity cytotoxicity against MDA-MB-231 MCF-7 cells. When was co-treated caspase inhibitor, Z-VAD-FMK, caspase-dependent apoptosis suppressed these found induce generation cytosolic calcium ions (Ca2+) reactive oxygen species (ROS), triggering endoplasmic reticulum (ER) stress via PERK-ATF4-CHOP axis. Hence, ER stressor thapsigargin (TG) synergized cells, while loss PERK or CHOP function phenomenon. shown oxidative NADPH oxidase 4 (NOX4) stimulate ROS production. NOX4 knockdown (KD) antioxidant (N-acetyl cysteine diphenyleneiodonium) such stress–mediated by inhibiting KA-enhanced activity, cytotoxicity, intracellular production treated radioresistant MDA-MB-231R MCF-7R combined 2 Gy radiation overcame upregulating modulating epithelial–mesenchymal transition (EMT) markers, E-cadherin, N-cadherin, vimentin. KD phenomenon due expression. Conclusions: conclusion, findings regulator promising

Language: Английский

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Antioxidant and anti‑inflammatory effects of a mixture of propolis, red bean and tomato extracts

International Journal of Functional Nutrition, Journal Year: 2024, Volume and Issue: 5(1)

Published: April 11, 2024

The aim of the present study was to investigate antioxidant and anti‑inflammatory effects a mixture propolis, red bean tomato extracts (PRTE). First, radical scavenging activities various combinations PRTE (1:1:1, M1‑PRTE; 1.5:1:0.5, M2‑PRTE; 1.5:0.5:1, M3‑PRTE; 1.2:0.9:0.9, M4‑PRTE) were estimated. M2‑PRTE exhibited optimal 2,2‑diphenyl‑1‑picrylhydrazyl (DPPH) 2,2'‑azino‑bis (3‑ethylbenzothiazoline‑6‑sulfonic acid) (ABTS) efficacy compared other ratios. DPPH ABTS (IC₅₀) 192.86±3.34 554.28±4.78 µg/ml, respectively. also restored levels superoxide dismutase, glutathione peroxidase which reduced by fine particulate matter in HaCaT cells. In addition, suppressed inflammatory mediators, such as nitric oxide, inducible oxide synthase, cyclooxygenase‑2 prostaglandin E2, increased lipopolysaccharide (LPS) stimulation RAW264.7 cells, dose‑dependent manner. significantly inhibited production pro‑inflammatory cytokines, including interleukin (IL)‑1β, tumor necrosis factor‑α IL‑6, LPS On whole, findings suggest that is an effective material for alleviating oxidative stress responses caused environmental pollution, it has potential use health functional foods.

Language: Английский

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Chemical Composition, Antioxidant, and Cytotoxic Effects of <em>Senna rugosa</em> Leaf and Root Extracts on Human Leukemia Cell Lines

Published: May 17, 2024

Senna rugosa is a species found in the Cerrado and used folk medicine as vermifuge treatment of poisonous snakebites accidents. In this work, we identified main secondary metabolites present ethanolic extracts leaves (ELSR) roots (ERSR) S. evaluated potential cytoprotective effect against cellular macromolecular damage, well cytotoxic properties on K562 Jurkat leukemic cell lines. The identification was done by liquid chromatography coupled with mass spectrometry. antioxidant activities were investigated direct ABTS•+ DPPH• radical scavenging methods, protection oxidative damage proteins DNA. healthy cells, isolated from human peripheral blood (PBMC) leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, dimeric trimeric procyanidins, while root profile shows obtusichromoneside 2-methoxystypandrone, stilbene naphthopyranones, flavanone derivatives. showed activity, IC50 4.86 ± 0.51 µg/mL 8.33 0.90 ABTS assay for ELSR ERSR, respectively. And assay, 19.98 1.96 13.37 1.05 ERSR. protected macromolecules at concentrations 5 µg/mL. cytotoxicity test strains observed after 24 48 hours treatment. After h, results line demonstrate 242.54 2.38 223.00 2.34 ERSR , While line, these 171.45 2.25 189.30 2.27 µg/mL, respectively Results PBMC viability, that selectivity Together, our reveal have completely distinct complex chemical compositions. This study expands repertoire compounds underscores their significant pharmacological conditions related to stress leukemia.

Language: Английский

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Cytotoxicity and antioxidant activities of bacteriocins extracted from novel marine lactic acid bacteria Lactococcus lactis NAN6399

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 20, 2024

This study aimed to evaluate the cytotoxicity, antioxidant, and antimicrobial activities of bacteriocins produced by novel marine lactic acid bacteria, specifically Lactococcus lactis NAN6399, isolated from Mediterranean Sea coast Alexandria. Additionally, comprehensive sequencing, analyses, protein identification this bacteriocin was conducted. The results indicated that isolate has a broad spectrum against tested bacterial indicators. Bacteriocin purified NAN6399 had molecular weight approximately 20 kDa designated as “lactococcin972”. Furthermore, cytotoxicity antioxidant were conducted on 3(4,5-dimethylthiazol-2-yl),2,5-diphenyl-tetrazolium bromide (MTT) assay Diphenyl picrylhydrazyl (DPPH) method, respectively. showed “lactococcin972” exhibited distinguished cytotoxic activity with inhibition rates 80% breast cancer (MCF-7) 30% lung (A549). reduction 72% DPPH. These findings suggest lactococcin972 significant potential therapeutic agents due their notable antimicrobial, cytotoxic, properties.

Language: Английский

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