Hyaluronic acid optimises therapeutic effects of hydrogen peroxide‐induced oxidative stress on breast cancer

Background: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. Methods: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund’s adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and a hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. Results: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1β, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. Conclusions: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.

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Conjugation with Methylsulfonylmethane Improves Hyaluronic Acid Anti-Inflammatory Activity in a Hydrogen Peroxide-Exposed Tenocyte Culture In Vitro Model

International Journal of Molecular Sciences ◽

10.3390/ijms21217956 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7956

Author(s):

Francesco Oliva ◽

Marialucia Gallorini ◽

Cristina Antonetti Lamorgese Passeri ◽

Clarissa Gissi ◽

Alessia Ricci ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Hyaluronic Acid ◽

Rotator Cuff ◽

Tendon Healing ◽

Rotator Cuff Tears ◽

Collagen Iii ◽

Anti Inflammatory ◽

Stress Damage

Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of disability in middle-aged individuals affected by nontraumatic shoulder dysfunctions. Our previous studies have demonstrated that four different hyaluronic acid preparations (HAPs), including Artrosulfur® hyaluronic acid (HA) (Alfakjn S.r.l., Garlasco, Italy), may exert a protective effect in human RCT-derived tendon cells undergoing oxidative stress damage. Recently, methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at evaluating three preparations (Artrosulfur® HA, MSM, and Artrosulfur® MSM + HA) in the recovery from hydrogen peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) and prostaglandin E2 (PGE2) modulation were investigated. In parallel, expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I and III were also examined. Results demonstrate that Artrosulfur® MSM + HA improves cell escape from oxidative stress by decreasing cytotoxicity and by reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 and MMP14 levels and enhances collagen III expression after 24 h, proteins globally related to rapid acceleration of the extracellular matrix (ECM) remodelling and thus tendon healing. By improving the anti-cytotoxic effect of HA, the supplementation of MSM may represent a feasible strategy to ameliorate cuff tendinopathies.

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Cell Cycle Arrest Induced by Hydrogen Peroxide Is Associated with Modulation of Oxidative Stress Related Genes in Breast Cancer Cells

Experimental Biology and Medicine ◽

10.3181/0903-rm-98 ◽

2009 ◽

Vol 234 (9) ◽

pp. 1086-1094 ◽

Cited By ~ 44

Author(s):

Pei-Jou Chua ◽

George Wai-Cheong Yip ◽

Boon-Huat Bay

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cell Cycle ◽

Hydrogen Peroxide ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Phase Cell ◽

Cycle Arrest ◽

Stress Related Genes

Depending on the amounts present, reactive oxygen species can exert either beneficial or deleterious effect to cells. In the present study, we observed a decrease in cell viability concomitant with an increase of malondialdehyde concentration in hydrogen peroxide (H2O2)-treated MCF-7 breast cancer cells. There was also a concurrent G1/S phase cell cycle arrest with increased apoptosis in H2O2-treated cells. Analysis of 84 oxidative stress related genes showed that five genes were significantly and differentially regulated, namely, Cytoglobin (CYGB), Forkhead box M1 (FOXM1), NADPH oxidase ( NOX5), Nudix (nucleoside diphosphate linked moiety X)-type motif 1 (NUDT1) and Selenoprotein P1 (SEPP1) genes with H2O2 treatment. It would seem that oxidative stress induces cell cycle arrest in the breast cancer by modulation of these genes. Manipulation of these genes, in particular FOXM1, a proliferation-specific gene associated with human malignancies, could stifle cancer progression and enhance the therapeutic efficacy of drugs which exert their effects by oxidative stress.

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Proteomic analysis of ginsenoside Re attenuates hydrogen peroxide-induced oxidative stress in human umbilical vein endothelial cells

Food & Function ◽

10.1039/c6fo00123h ◽

2016 ◽

Vol 7 (5) ◽

pp. 2451-2461 ◽

Cited By ~ 10

Author(s):

Gui-dong Huang ◽

Xian-feng Zhong ◽

Ze-yuan Deng ◽

Rong Zeng

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Endothelial Cells ◽

Proteomic Analysis ◽

Active Component ◽

Umbilical Vein ◽

Therapeutic Effects ◽

Ginsenoside Re ◽

System P ◽

Umbilical Vein Endothelial Cells

Ginsenoside Re is an active component in ginseng that has attracted much attention because of its evident therapeutic effects on the cardiovascular system.

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Hyaluronic Acid Improves Hydrogen Peroxide Modulatory Effects on Calcium Channel and Sodium-Potassium Pump in 4T1 Breast Cancer Cell Line

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8681349 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ardeshir Abbasi ◽

Nafiseh Pakravan ◽

Zuhair Mohammad Hassan

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Hyaluronic Acid ◽

Cancer Cells ◽

Breast Cancer Cell Line ◽

Cancer Cell Line ◽

Sodium Potassium ◽

Normal Cells ◽

4T1 Breast Cancer ◽

Sodium And Potassium

Maintaining homeostasis of ion concentrations is critical in cancer cells. Under hypoxia, the levels of channels and pumps in cancer cells are more active than normal cells suggesting ion channels as a suitable therapeutic target. One of the contemporary ways for cancer therapy is oxidative stress. However, the effective concentration of oxidative stress on tumor cells has been reported to be toxic for normal cells as well. In this study, we benefited from the modifying effects of hyaluronic acid (HA) on H2O2, as a free radical source, to make a gradual release of oxidative stress on cancer cells while preventing/decreasing damage to normal cells under normoxia and hypoxic conditions. To do so, we initially investigated the optimal concentration of HA antioxidant capacity by the DPPH test. In the next step, we found optimum H2O2 dose by treating the 4T1 breast cancer cell line with increasing concentrations (0, 10, 20, 50,100, 200, 500, and 1000 μM) of H2O2 alone or H2O2 + HA (83%) for 24 hrs. The calcium channel and the sodium-potassium pumps were then evaluated by measuring the levels of calcium, sodium, and potassium ions using an atomic absorption flame spectrophotometer. The results revealed that treatment with H2O2 or H2O2+ HA led to an intracellular increase of calcium, sodium, and potassium in the normoxic and hypoxic circumstances in a dose-dependent manner. It is noteworthy that H2O2 + HA treatment had more favorable and controllable effects compared with H2O2 alone. Moreover, HA optimizes the antitumor effect of oxidative stress exerted by H2O2 making H2O2 + HA suitable for clinical use in cancer treatment along with chemotherapy.

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Hyaluronic acid optimizes therapeutic effects of Hydrogen peroxide-induced oxidative stress on breast cancer

10.21203/rs.3.rs-21485/v1 ◽

2020 ◽

Author(s):

Ardeshir Abbasi ◽

Nafiseh Pakravan ◽

Zuhair Hassan

Keyword(s):

Oxidative Stress ◽

Hyaluronic Acid ◽

Cancer Cells ◽

Mononuclear Cells ◽

Phase Cell ◽

High Dose ◽

Therapeutic Effects ◽

Mrna Levels ◽

Dependent Manner

Abstract Background and Purpose: Distinguishing the multiple effects of reactive oxygen species (ROS) on cancer cells is important to understand their role in tumour biology. Conversely, elevated levels of ROS-induced oxidative stress can induce cancer cell death. However, some anti-oxidative or ROS-mediated oxidative therapies have also yielded beneficial effects.Experimental approach: To better define the effects of oxidative stress, in vitro experiments were conducted on 4T1 and splenic mononuclear cells (MNCs) under hypoxic and normoxic conditions. Furthermore, H2O2 [10-1000μM], was used as a ROS source alone or in combination with hyaluronic acid (HA), which is frequently used as drug delivery vehicle.Key Results: Our results indicate that treatment of cancer cells with H2O2+HA was significantly more effective than H2O2 alone. In addition, treatment with H2O2+HA led to increased apoptosis, decreased proliferation, and multi-phase cell cycle arrest in 4T1 cells in a dose-dependent manner under normoxic or hypoxic conditions. Also, migratory tendency and the mRNA levels of VEGF, and MMP-2,9 were significantly decreased. Of note, HA treatment combined with 100-1000μM H2O2+ caused more damage to MNCs as compared to treatment with lower concentrations [10-50μM]. Based on these results we propose to administer high dose H2O2+HA [100-1000μM] for intra-tumoral injection and low doses for systemic administration.Conclusions & Implications: Intra-tumoral route could have toxic and inhibitory effects not only on the tumour but also on residential myeloid cells defending it, whereas systemic treatment could stimulate peripheral immune responses against the tumour. More in vivo research is required to confirm this hypothesis.

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Novel hyaluronic acid-coated polymeric micelles with ROS scavenging to encapsulate statins for alleviating atherosclerosis

10.21203/rs.3.rs-89851/v1 ◽

2020 ◽

Author(s):

Dan Mu ◽

Jianhui Li ◽

Yu Qi ◽

Xuan Sun ◽

Yihai Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Hyaluronic Acid ◽

Polymeric Micelles ◽

Therapeutic Effects ◽

Ros Scavenging ◽

Poly Ethylene ◽

Major Factors ◽

Inflammatory Macrophages ◽

And Oxidative Stress ◽

Micelle System

Abstract Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the SIM-loaded micelles demonstrated remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system can synchronically alleviate the accumulation of macrophages and oxidative stress, providing a promising and innovative option against atherosclerosis.

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Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00744-w ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Dan Mu ◽

Jianhui Li ◽

Yu Qi ◽

Xuan Sun ◽

Yihai Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Hyaluronic Acid ◽

Polymeric Micelles ◽

Therapeutic Effects ◽

Low Cytotoxicity ◽

High Cytotoxicity ◽

Major Factors ◽

Inflammatory Macrophages ◽

And Oxidative Stress ◽

Micelle System

AbstractInflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.

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