scholarly journals Natural Phenolic Acid, Product of the Honey Bee, for the Control of Oxidative Stress, Peritoneal Angiogenesis, and Tumor Growth in Mice

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5583
Author(s):  
Nada Oršolić ◽  
Martina Kunštić ◽  
Marina Kukolj ◽  
Dyana Odeh ◽  
Daniela Ančić
Keyword(s):  
Oxidative Stress ◽  
Tumor Growth ◽  
Macrophage Polarization ◽  
Differential Count ◽  
Swiss Albino Mouse ◽  
Acid Product ◽  
M1 Macrophages ◽  
Promising Target ◽  
Ehrlich Ascites ◽  
Eat Cells

Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.

scholarly journals Cytokine profile of Ehrlich ascites tumor treated withBothrops jararacavenom

2002 ◽  
Vol 11 (4) ◽  
pp. 197-201 ◽  
Author(s):  
Reinaldo J. da Silva ◽  
Márcia G. da Silva ◽  
Lízia C. Vilela ◽  
Denise Fecchio
Keyword(s):  
Tumor Growth ◽  
Antitumor Effect ◽  
Cytokine Profile ◽  
Ehrlich Ascites Tumor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ascites Tumor ◽  
Ehrlich Ascites ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Eat Cells

We previously demonstrated thatBothrops jararacavenom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated withBjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated withBjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme-linked immunosorbent assay for interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-13, and tumor necrosis factor-α (TNF-α) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal-Wallis and Dunn's tests at the 5% level of significance. We observed that EAT implantation induces IL-6 production on the 11th and 14th days of tumor growth, IL-10 on the 11th day and TNF-α on the 14th day. The treatment withBjV suppresses production of these cytokines. In addition, IL-13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL-6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect ofBjV.

scholarly journals Modulation of Cytokines Production by Indomethacin Acute Dose during the Evolution of Ehrlich Ascites Tumor in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Luciana Boffoni Gentile ◽  
Nicolle Queiroz-Hazarbassanov ◽  
Cristina de Oliveira Massoco ◽  
Denise Fecchio
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Cytokine Profile ◽  
Ehrlich Ascites Tumor ◽  
The Other ◽  
Ascites Tumor ◽  
Ehrlich Ascites ◽  
Eat Cells ◽  
Cox2 Inhibitor ◽  
Indomethacin Treatment

The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNFα, IL-1α, IL-2, IL-4, IL-6, IL-10, and IL-13 and PGE2level in peritoneal cavity. The results have shown that EAT induces PGE2production and increases tumor cells number from the 10th day. The cytokine profile showed EAT induces production of IL-6 from 10th day and of IL-2 on 13th day; the other studied cytokines were not affected in a significant way. The indomethacin treatment of EAT-bearing mice inhibited the tumor growth and PGE2synthesis from the 10th day. In addition, the treatment of EAT-bearing mice with indomethacin has stimulated the IL-13 production and has significantly inhibited IL-6 in the 13th day of tumor growth. Taken together, the results have demonstrated that EAT growth is modulated by PGE2and the inhibition of the tumor growth could be partly related to suppression of IL-6 and induction of IL-13.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

scholarly journals Iron Released after Cryo-Thermal Therapy Induced M1 Macrophage Polarization, Promoting the Differentiation of CD4+ T Cells into CTLs

2021 ◽  
Vol 22 (13) ◽  
pp. 7010
Author(s):  
Shicheng Wang ◽  
Man Cheng ◽  
Peng Peng ◽  
Yue Lou ◽  
Aili Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Immunity ◽  
Macrophage Polarization ◽  
Thermal Therapy ◽  
High Plasticity ◽  
Antitumor Effects ◽  
M1 Macrophages ◽  
Splenic Macrophages ◽  
M1 Macrophage

Macrophages play critical roles in both innate and adaptive immunity and are known for their high plasticity in response to various external signals. Macrophages are involved in regulating systematic iron homeostasis and they sequester iron by phagocytotic activity, which triggers M1 macrophage polarization and typically exerts antitumor effects. We previously developed a novel cryo-thermal therapy that can induce the mass release of tumor antigens and damage-associated molecular patterns (DAMPs), promoting M1 macrophage polarization. However, that study did not examine whether iron released after cryo-thermal therapy induced M1 macrophage polarization; this question still needed to be addressed. We hypothesized that cryo-thermal therapy would cause the release of a large quantity of iron to augment M1 macrophage polarization due to the disruption of tumor cells and blood vessels, which would further enhance antitumor immunity. In this study, we investigated iron released in primary tumors, the level of iron in splenic macrophages after cryo-thermal therapy and the effect of iron on macrophage polarization and CD4+ T cell differentiation in metastatic 4T1 murine mammary carcinoma. We found that a large amount of iron was released after cryo-thermal therapy and could be taken up by splenic macrophages, which further promoted M1 macrophage polarization by inhibiting ERK phosphorylation. Moreover, iron promoted DC maturation, which was possibly mediated by iron-induced M1 macrophages. In addition, iron-induced M1 macrophages and mature DCs promoted the differentiation of CD4+ T cells into the CD4 cytolytic T lymphocytes (CTL) subset and inhibited differentiation into Th2 and Th17 cells. This study explains the role of iron in cryo-thermal therapy-induced antitumor immunity from a new perspective.

scholarly journals Kras-driven intratumoral heterogeneity triggers infiltration of M2 polarized macrophages via the circHIPK3/PTK2 immunosuppressive circuit

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Theodora Katopodi ◽  
Savvas Petanidis ◽  
Kalliopi Domvri ◽  
Paul Zarogoulidis ◽  
Doxakis Anestakis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Quantitative Polymerase Chain Reaction ◽  
Macrophage Polarization ◽  
Metastatic Potential ◽  
Intratumoral Heterogeneity ◽  
M2 Macrophage

AbstractIntratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.

scholarly journals Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) modulates M1 macrophage polarization through TLR4/MAPK/NF-κB signaling pathways on murine macrophages

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Se Hyang Hong ◽  
Jin Mo Ku ◽  
Ye Seul Lim ◽  
Hyo In Kim ◽  
Yong Cheol Shin ◽  
...  
Keyword(s):  
Digestive Enzymes ◽  
Macrophage Polarization ◽  
Water Extract ◽  
Cervus Nippon ◽  
No Production ◽  
M1 Macrophages ◽  
Murine Macrophages ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Cytokine Levels

The objective of this study was to investigate the effects of Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) on the promotion of M1 macrophage polarization in murine macrophages. Macrophages polarize either to one phenotype after stimulation with LPS or IFN-γ or to an alternatively activated phenotype that is induced by IL-4 or IL-13. Cell viability of RAW264.7 cells was determined by WST-1 assay. NO production was measured by Griess assay. IL-6, IL-12, TNF-α, and iNOS mRNA levels were measured by RT-PCR. IL-6, IL-12, and IL-10 cytokine levels were determined by ELISA. TLR4/MAPK/NF-κB signaling in RAW264.7 cells was evaluated by western blotting. The level of NF-κB was determined by immunoblotting. CE induced the differentiation of M1 macrophages. CE promoted M1 macrophages to elevate NO production and cytokine levels. CE-stimulated M1 macrophages had enhanced IL-6, IL-12, and TNF-α. CE promoted M1 macrophages to activate TLR4/MAPK/NF-κB phosphorylation. M2 markers were downregulated, while M1 markers were upregulated in murine macrophages by CE. Consequently, CE has immunomodulatory activity and can be used to promote M1 macrophage polarization through the TLR4/MAPK/NF-κB signaling pathways.

scholarly journals Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization

2020 ◽  
Vol 19 ◽  
pp. 153473542094967
Author(s):  
Min Kyoon Kim ◽  
Yesl Kim ◽  
SeungHwa Park ◽  
Eunju Kim ◽  
Yerin Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
High Fat Diet ◽  
Tumor Volume ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
High Fat ◽  
Low Intensity ◽  
M2 Macrophage Polarization ◽  
Low Intensity Exercise

Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.

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