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Natural ingredients have been used for centuries for skin care purposes. Nowadays, they are becoming more prevalent in formulations, due to consumers' concerns about synthetic ingredients/chemical substances. The main benefits reported for plant extracts, used in skin care, include antioxidant and antimicrobial activities and tyrosinase inhibition effect. In this review, some examples of plants from Portuguese flora, whose extracts have shown good properties for skin care are presented. However, despite the known properties of plant extracts, few studies reported the development of formulations with them. More work in this field can be accomplished to meet consumer demand.

P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, like melanomas. Here, we investigated if P-cadherin expression would interfere with the normal adhesion complex and which were the cellular/molecular consequences, constituting, in this way, a new mechanism by which E-cadherin invasive-suppressor function was disrupted. Using breast TNBC models, we demonstrated, for the first time, that P-cadherin co-localizes with E-cadherin, promoting cell invasion due to the disruption caused in the interaction between E-cadherin and cytoplasmic catenins. P-cadherin also induces cell migration and survival, modifying the expression profile of cells expressing wild-type E-cadherin and contributing to alter their cellular behaviour. Additionally, E- and P-cadherin co-expressing cells significantly enhanced in vivo tumour growth, compared with cells expressing only E- or only P-cadherin. Finally, we still found that co-expression of both molecules was significantly correlated with high-grade breast carcinomas, biologically aggressive, and with poor patient survival, being a strong prognostic factor in this disease. Our results show a role for E- and P-cadherin co-expression in breast cancer progression and highlight the potential benefit of targeting P-cadherin in the aggressive tumours expressing high levels of this protein.

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours. IntroductionClassical cadherins, such as E-cadherin, N-cadherin and Pcadherin, are the best characterized subgroup of adhesion proteins; they mediate calcium-dependent cell-cell bonds when they are localized to the adherens-type junctions. These cellular structures are found near to the apical surface of polarized epithelial cells, where E-cadherin (or epithelial cadherin) is the typical adhesion molecule present. However, other cadherins are found in similar structures in various cell types [1]. P-cadherin (or placental cadherin) was the third classical cadherin to be identified and characterized in the mouse visceral endoderm cell line PSA5-E [2,3], and it is this protein that constitutes the main subject of this review. Despite its name, P-cadherin is not expressed in human placenta [4]; its name results from the fact that this molecule was originally observed to be highly expressed in mouse placenta throughout pregnancy [2,4].The gene encoding P-cadherin (CDH3) is far less well characterized than is CDH1 (the gene that encodes E-cadherin), although they share 66% homology. It also maps to chromosome 16q22.1, a region that contains a cluster of several cadherin genes, just 32 kilobases upstream of the gene encoding human E-cadherin [5,6]. Mutations in the CDH3 gene have been reported to be responsible for congenital hypotrichosis associated with juvenile macular dystrophy, which is a rare autosomal-recessive disorder characterized by abnormal growth of scalp hair, followed by progressive macular retinal degeneration that leads to early blindness [7].The mature P-cadherin glycoprotein has a molecular weight of 118 kDa, and its structure is similar to that of classical cadherins but different from those of E-cadherin and Ncadherin in terms of immunological specificity and molecular mass [2]. It is comprised of three distinct domains (extracellular, transmembrane and cytoplasmic) and it mainly, but not exclusively, promotes homotypic interactions (between cadherins of the same type) [1,2]. The aminoterminal domain is essential for the creation of lateral dimmers that act together in a zipper-like structure between neighbouring cells (Figure 1) [8].The function and strength of P-cadherin mediated adhesion probably depends on its dynamic association with a group of cytoplasmic molecules, called catenins. These molecules serve to link the cadherin cytoplasmic t...

Epithelial–mesenchymal transition (also known as EMT) is a fundamental mechanism occurring during embryonic development and tissue differentiation, being also crucial for cancer progression. Actually, the EMT program contributes to the dissemination of cancer cells from solid tumors and to the formation of micro-metastasis that subsequently develop into clinically detectable metastases. Besides being a process that is defined by the progressive loss of epithelial cell characteristics and the acquisition of mesenchymal features, EMT has also been implicated in therapy resistance, immune escape, and maintenance of cancer stem cell properties, such as self-renewal capacity. However, the majority of the studies usually neglect the progressive alterations occurring during intermediate EMT states, which imply a range of phenotypic cellular heterogeneity that can potentially generate more metastable and plastic tumor cells. In fact, few studies have tried to identify these transitory states, partly due to the current lack of a detailed understanding of EMT, as well as of reliable readouts for its progression. Herein, a brief review of evidences is presented, showing that P-cadherin expression, which has been already identified as a breast cancer stem cell marker and invasive promoter, is probably able to identify an intermediate EMT state associated with a metastable phenotype. This hypothesis is based on our own work, as well as on the results described by others, which suggest the use of P-cadherin as a promising EMT marker, clearly functioning as an important clinical prognostic factor and putative therapeutic target in breast carcinogenesis.

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The use of magnetic nanorobots to activate chemotherapeutic prodrugs represents a promising alternative to current chemotherapeutic treatments. Here, a hybrid nanowire (NW) for targeted bioorthogonally driven activation of the latent chemotherapeutic prodrug 5‐fluoro‐1‐propargyl‐uracil (Pro‐5‐FU) in in vitro and in vivo cancer models is proposed. The NWs are composed of magnetic iron (Fe) and palladium (Pd), a known bioorthogonal catalyst. In vitro tests with a cancer cell line showed no significant cytotoxic effect by the NWs. In contrast, NWs combined with Pro‐5‐FU lead to a significant reduction of cell viability, similarly to the one induced by its active chemotherapeutic counterpart 5‐fluorouracil (5‐FU). The reduction in cell viability is attributed to the catalytic activation of Pro‐5‐FU into 5‐FU. To demonstrate their targeted therapeutic abilities, magnetic fields are used to attract the FePd NWs to a predefined area within a cultured cancer cell population, causing a local Pro‐5‐FU activation, and subsequent cell death in this region. As a proof of concept, NWs are injected in cancer tumor xenografts. The intraperitoneal injection of Pro‐5‐FU significantly retards tumour growth without causing significant side effects. This work presents a novel chemotherapeutic approach combining nanorobotics and bioorthogonal activation of prodrugs as an efficient alternative to conventional chemotherapy.