Characterization of the inflammatory response during Ehrlich ascitic tumor development

Fernandes, Patrícia Dias; Guerra, Fabiana Sélos; Sales, Natália M.; Sardella, Thais B.; Jancar, Sônia; Neves, Josiane S.

doi:10.1016/j.vascn.2014.09.001

Cited by 21 publications

(23 citation statements)

References 28 publications

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“…In addition to neutrophils, macrophages express MPO, suggesting that the inhibition of MPO activity by quercetin treatment could also involve the reduction of macrophage counts. This is consistent with the demonstration that Ehrlich tumor cells induce the recruitment of monocytes, which could differentiate into macrophages [ 42 ]. Treatment with quercetin also inhibits MPO activity in vitro [ 44 ] and also the neutrophil recruitment in vivo and neutrophil chemotaxis in vitro induced by chemokines, fMLP (formyl-methionyl-leucyl-phenylalanine) and leukotriene B 4 [ 40 ].…”

Section: Resultssupporting

confidence: 92%

“…There is evidence that ascitic Ehrlich tumor induces the recruitment to the peritoneal cavity of mice of cellular populations consistent with dendritic cells, monocytes, and neutrophils [ 42 ]. In the present study, it was observed that Ehrlich tumor injection in the paw induces an increase of myeloperoxidase (MPO) activity and daily treatment with quercetin (100 mg/kg, i.p.)…”

Section: Resultsmentioning

confidence: 99%

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Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

Calixto-Campos

Corrêa

Carvalho

et al. 2015

Analytical Cellular Pathology

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Cancer pain directly affects the patient's quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti-inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor-induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1β and TNFα and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

Calixto-Campos

Corrêa

Carvalho

et al. 2015

Analytical Cellular Pathology

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“…Tumor inoculation was similar in the Fernandes et al [ 8 ] with the same number of tumor cells as in Patra et al [ 9 ].…”

Section: Main Textmentioning

confidence: 93%

Tumor growth activity of duloxetine in Ehrlich carcinoma in mice

et al. 2018

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ObjectiveThe objective of this study was to analyze whether duloxetine influences tumor growth in Ehrlich carcinoma. The mice were administered 5 or 30 mg/kg of duloxetine or saline solution. All animals were inoculated with tumor cells. The tumor progression was evaluated by body weight, abdominal circumference, ascites volume and tumor cell count. The effect of duloxetine on immune response was evaluated by lymphoid cells, nitric oxide (NO) production, arginase and superoxide dismutase (SOD) activity and the spleen immunophenotyping.ResultsThere was no difference between the groups regarding weight, abdominal circumference, ascites volume and number of tumor cells. Duloxetine increased the cells of the inguinal lymph node. There was no difference in the number of cells in the bone marrow and spleen. Ascites SOD activity was greater in Duloxetine groups. There were no differences in the levels of NO, nitrite, and arginase. The number of antibody for CD3 (CD3+), CD4+, CD8+ and CD28+ cells was lower in the duloxetine groups. In conclusion, duloxetine has no direct effect on tumor growth and does not alter immunity. The drug increased the SOD that fights free radicals and led the migration of lymphocytes, suggesting that duloxetine could be used in tumor-bearing individuals.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3655-4) contains supplementary material, which is available to authorized users.

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“…The cytotoxicity assay in mouse erythrocytes allows us to evaluate the potential of a drug to cause damage to the cell’s plasma membrane, pore formation or the measurement of cell permeability [ 25 ]. In addition, erythrocytes are known to be targets of antineoplastic drugs [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

Santos

Brito

Ferreira

et al. 2018

IJMS

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Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

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Characterization of the inflammatory response during Ehrlich ascitic tumor development

Cited by 21 publications

References 28 publications

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

Tumor growth activity of duloxetine in Ehrlich carcinoma in mice

Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

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