Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A2 (PLA2) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA2 are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA2 leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA2 and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA2 in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA2 and the approaches that could be used in order to resume the anti-PLA2 function of Annexin A1.

Triple negative breast cancers (TNBC) are heterogeneous and aggressive pathologies, with distinct morphological and clinical characteristics associated with their genetic diversity, epigenetics, transcriptional changes and aberrant molecular patterns. Treatment with anti-neoplastic drugs exerts systemic effects with low specificity, and incipient improvement in overall survival due to chemoresistance and recurrence. New alternatives for TNBC treatment are urgent and parthenolide or its analogues have been explored. Parthenolide is a sesquiterpene lactone with promising antitumor effects against TNBC cell lines. This review highlights the importance of parthenolide and its analogue drugs in TNBC treatment.

Background: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC). background: Effective cancer treatment still challenges medicine, since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm and the outcome of patients, especially those with advanced castration resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as DOC. Objective: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells. objective: This study investigates 4-nerolidylcatechol (4-NC)’s synergistic potentiation with DOC in inhibiting androgen-independent PCa cells. Methods: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). method: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). Results: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4-NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells. Conclusion: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells. other: Our results pave the way for new therapeutic strategies to be incorporated in the treatment of PCa.

Soil physical structure is related to porous space dynamics, which is affected by pedogenetic conditions, land uses, and agricultural practices. Thus, the objective of this work was to evaluate physical and structural attributes of Cambissolos under different uses in the Terra de Esperança Settlement Project, in Chapada do Apodi, Governor Dix-Sept Rosado, Rio Grande do Norte, Brazil, and detect the most sensitive attributes for the distinction of environments using multivariate analysis. The study areas with different land uses were: Native Forest Area 1 (NFA1), Native Forest Area 2 (NFA2), Native Forest Area 3 (NFA3) (reference areas), Conventional Management Area (CMA) Agroecological Area (AEA), and Cajaraneira (Spondia sp.) Orchard Area (COA). Areas with agricultural uses were characterized through physical and structural analyses, using disturbed and undisturbed soil samples collected from their 0.00-0.10, 0.10-0.20, and 0.20-0.30 m soil layers. The soil classes of the areas, according to the Brazilian Soil Classification System (SiBCS) were Cambissolo Haplico Carbonatico vertissolico (NFA1); Cambissolo Haplico Ta Eutrofico tipico (NFA2 and COA); Cambissolo Haplico Ta Eutrofico vertissolico (NFA3); and Cambissolo Haplico Carbonático tipico (CMA and AEA). The results of the attributes analyzed were expressed as mean of three replications per soil layer of each area, using multivariate analysis. Soil textures varied from sandy clay loam to clay. The total sand fraction presented negative correlations with clay dispersed in water, gravimetric moisture (GM), volumetric moisture (VM), total porosity determined (TPd) and microporosity (MiP); and positive correlations with soil density (SD), and basic infiltration rate (BIR), denoting pedogenetic influence. The SD presented significant correlation with GM, VM, TPd, MiP, macroporosity (MaP), aeration porosity (AP) and BIR, denoting its importance for the physical structure of the soil, and its dynamics. The most relevant attributes for the discrimination of the soil physical structure were the inorganic fractions clay and sand, porosity, degree of flocculation, aggregates, and soil mechanical resistance to penetration. The physical and structural attributes of the Cambissolos Haplicos were generally preserved, when compared to the current conditions of the NFAs, despite the different land use and managements. However, the soils of NFA1 (0.20-0.30 m layer), CMA, and AEA areas indicate fragility in aggregate stability and degree of flocculation due to the predominance of the sand fraction. The COA presented more favorable physical and structural conditions to the development of agricultural crops, especially on the surface layers, mostly influenced by their clay, TPd, AP, GM, VM, and soil mechanical resistance to penetration.