Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell

Gimenes, Sarah Natalie Cirilo; Lopes, Daiana Silva; Alves, Patrícia Terra; Azevedo, Fernanda Van Petten de Vasconcelos; Vecchi, Lara; Goulart, Luíz Ricardo; Santos, André Luíz Quagliatto; Brites, Vera Lucia de Campos; Teixeira, Thaíse Lara; Silva, Cláudio V. da; Dias, Matheus Henrique; Teixeira, Samuel Cota; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Oliveira, Rita C. M.; Rodrigues, Veridiana de Melo

doi:10.1038/s41598-017-07082-2

Cited by 20 publications

(9 citation statements)

References 88 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The aortic ring assay is a well-accepted method for evaluating angiogenesis ( Gimenes et al, 2017 ; Weng et al, 2017 ): thoracic aortas were isolated, cut into rings, and used in the aortic ring assay as previously described. Microvessel sprouts began to merge at day 3 in aortic rings from mice treated with either NSD or HSD for consecutive 12 week.…”

Section: Resultsmentioning

confidence: 99%

Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial Dysfunction

Chen

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Backgrounds and Aims: Na+ is an important nutrient and its intake, mainly from salt (NaCl), is essential for normal physiological function. However, high salt intake may lead to vascular injury, independent of a rise in blood pressure (BP). Canonical NALP3 inflammasome activation is a caspase-1 medicated process, resulting in the secretion of IL-18 and IL-1β which lead to endothelial dysfunction. However, some researches uncovered a direct and inflammasome-independent role of NALP3 in renal injury. Thus, this study was designed to investigate the possible mechanisms of NALP3 in high salt induced endothelial dysfunction.Methods and Results: Changes in endothelial function were measured by investigating mice (C57BL/6J, NALP3-/- and wild-type, WT) fed with normal salt diet (NSD) or high salt diet (HSD) for 12W, and thoracic aortic rings from C57BL/6J mice cultured in high-salt medium. Changes of tube formation ability, intracellular reactive oxygen species (ROS), and NALP3 inflammasome expression were detected using mouse aortic endothelial cells (MAECs) cultured in high-salt medium. Consumption of HSD for 12W did not affect BP or body weight in C57BL/6J mice. Endothelium-dependent relaxation (EDR) decreased significantly in C57BL/6J mice fed with HSD for 12W, and in isolated thoracic aortic rings cultured in high-salt medium for 24 h. Results from the aortic ring assay also revealed that the angiogenic function of thoracic aortas was impaired by either consumption of HSD or exposure to high-salt medium. NALP3-/- mice fed with HSD showed a relatively mild decrease in EDR function when compared with WT mice. Tube length of thoracic aortic rings from NALP3-/- mice was longer than those from WT mice after receiving high-salt treatment. Inhibiting NALP3 with a NALP3 antagonist, small interfering (si) RNA experiments using si-NALP3, and decomposing ROS significantly improved tube formation ability in MAECs under high salt medium. NALP3 expression was increased in MAECs cultured with high salt treatment and inhibiting NALP3 reversed the down-regulation of p-eNOS induced by high salt in MAECs.Conclusion: High salt intake impairs endothelial function, which is at least in part mediated by increasing NALP3 expression.

show abstract

Section: Resultsmentioning

confidence: 99%

Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial Dysfunction

Chen

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Gimenes et al. reported that γCdcPLI1 inhibits the activity of PLA 2 in a PI3K/Akt dependent manner, possibly by interfering with the expression of Akt1/3 and PI3KR1 ( 68 ). Besides, PI3K also funds the activity of Crotoxin B, a catalytically active subunit IIA sPLA ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas

Liu²,

Wang³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesis-related gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease.

show abstract

“…These fragments were treated over 9 days, at 1-day intervals. Subsequently, the aortic rings were photographed using an inverted optical microscope (Nikon Eclipse TS100) [ 32 ] and the sprouting length was expressed in pixels for quantitative analysis in ImageJ software, as previously described by [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

A New Approach to Inhibiting Triple-Negative Breast Cancer: In Vitro, Ex Vivo and In Vivo Antiangiogenic Effect of BthTx-II, a PLA2-Asp-49 from Bothrops jararacussu Venom

et al. 2022

View full text Add to dashboard Cite

Phospholipases A2 (PLA2) represent a superfamily of enzymes widely distributed in living organisms, with a broad spectrum of pharmacological activities and therapeutic potential. Anti-angiogenic strategies have become one of the main tools in fighting cancer. In this sense, the present work reports the inhibition of tumor angiogenesis induced by Asp-49 BthTX-II using in vitro, ex vivo and in vivo approaches. We demonstrate that BthTx-II inhibited cell adhesion, proliferation, and migration of human umbilical vein endothelial cells (HUVEC), as well as caused a reduction in the levels of endothelial growth factor (VEGF) during in vitro angiogenesis assays. BthTx-II was also able to inhibit the sprouting angiogenic process, by the ex vivo germination assay of the aortic ring; in addition, this toxin inhibited the migration and proliferation of HUVEC in co-culture with triple-negative breast cancer cells (e.g., MDA-MB-231 cells). Finally, in vivo tumor suppression and anti-angiogenic activities were analyzed using MDA-MB-231 cells with Matrigel injected into the chorioallantoic membrane of chicken embryo (CAM) for 7 days treatment with BthTx-II, showing a considerable reduction in vessel caliber, on the size and weight of tumors. Together, these results suggest an important antiangiogenic and antitumor role for BthTx-II, as a potential prototype for the development of new tools and antitumor drugs in cancer therapy.

show abstract

Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell

Cited by 20 publications

References 88 publications

Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial Dysfunction

Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial Dysfunction

Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas

A New Approach to Inhibiting Triple-Negative Breast Cancer: In Vitro, Ex Vivo and In Vivo Antiangiogenic Effect of BthTx-II, a PLA2-Asp-49 from Bothrops jararacussu Venom

Contact Info

Product

Resources

About