Flores para el tratamiento del cáncer: de la belleza al deber

Cancer is a worldwide disease that affects millions of people every year. Although there are several approved chemotherapeutic drugs for cancer treatment, there is s constant search for new molecules. This search is supported by the need of new molecules that could target cancer cells specifically reducing side effects or that could act synergistically with approved anticancer drugs. In this review, research on flower extracts and flower-derived molecules is presented.El cáncer es una enfermedad mundial que afecta a millones de personas cada año. Aunque existen varios fármacos quimioterapéuticos aprobados para el tratamiento del cáncer, existe una búsqueda constante de nuevas moléculas. Esta búsqueda está respaldada por la necesidad de nuevas moléculas que puedan apuntar a las células cancerosas reduciendo específicamente los efectos secundarios o que puedan actuar de manera sinérgica con los medicamentos contra el cáncer aprobados. En esta revisión, se presenta la investigación sobre extractos de flores y moléculas derivadas de flores

SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer

International audienceStudies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI), which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol. In the context of atherosclerosis, SR-BI has been implicated in the regulation of intracellular signaling, lipid accumulation, foam cell formation, and cellular apoptosis. Furthermore, since lipid metabolism is a relevant target for cancer treatment, recent studies have focused on examining the role of SR-BI in this pathology. While signaling pathways have initially been explored in non-tumoral cells, studies with cancer cells have now demonstrated SR-BI's function in tumor progression. In this review, we will discuss the role of SR-BI during tumor development and malignant progression. In addition, we will provide insights into the transcriptional and post-transcriptional regulation of the SCARB1 gene. Overall, studying the role of SR-BI in tumor development and progression should allow us to gain useful information for the development of new therapeutic strategies

Identificación de dianas moleculares del cáncer de mama que interactúan con moléculas presentes en los frutos de Antidesma bunius: análisis basado en farmacología de red in silico

The fruit of Antidesma bunius has both medicinal and edible properties. In previous studies, the fruit extract of A. bunius showed anti-proliferation activity on breast cancer cells, but its functional components and anti-tumor mechanism are still unclear. In this research, the main active components of A. bunius fruits (detected by UHPLC-MS/MS) and the corresponding targets were analyzed by network pharmacology method, and its interactions were verified by molecular docking to explore the possible tumor suppressor mechanisms. A total of 24 active chemical components were screened from fruits extract of A. bunius，and 44 targets genes were intersected with breast cancer, among them, AKT1, ESR1, EGFR, EP300, ERBB2 and AR were the top core targets．The GO enrichment of target genes mainly involved processes of cellular lipid metabolism, response to hormones, tube development, and KEGG pathway analysis centers in cancer pathways present in  breast, pancreatic and non-small cell lung cancer．The flavonoids in the fruits of A. bunius showed strong binding to the core targets by molecular docking analysis. These results strongly suggest that the flavonoids in the fruit of A. bunius can inhibit proliferation of breast cancer through multiple targets, mainly by ERK and PI3K-AKT pathways.El fruto de Antidesma bunius tiene propiedades medicinales y comestibles. En estudios anteriores, el extracto de fruta de A. bunius mostró actividad antiproliferativa en las células de cáncer de mama, pero sus componentes funcionales y mecanismo antitumoral aún no están claros. En esta investigación se analizaron los principales componentes activos de los frutos de A. bunius (detectados por UHPLC-MS / MS) y las dianas correspondientes mediante el método de farmacología en red, y se verificaron sus interacciones mediante acoplamiento molecular para explorar los posibles mecanismos supresores de tumores. Se seleccionaron un total de 24 componentes químicos activos del extracto de frutas de A. bunius, y 44 genes diana se cruzaron con el cáncer de mama, entre ellos, AKT1, ESR1, EGFR, EP300, ERBB2 y AR fueron los principales objetivos principales. de los genes diana involucraban principalmente procesos de metabolismo de lípidos celulares, respuesta a hormonas, desarrollo de tubos y centros de análisis de la vía KEGG en las vías del cáncer presentes en el cáncer de mama, páncreas y pulmón de células no pequeñas．Los flavonoides en los frutos de A. bunius mostraron fuertes unión a los objetivos centrales mediante análisis de acoplamiento molecular. Estos resultados sugieren fuertemente que los flavonoides en la fruta de A. bunius pueden inhibir la proliferación del cáncer de mama a través de múltiples dianas, principalmente por las vías ERK y PI3K-AKT

Endothelial caveolin-1 plays a major role in the development of atherosclerosis.

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Oxidized Products of α-Linolenic Acid Negatively Regulate Cellular Survival and Motility of Breast Cancer Cells

International audienceDespite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively. In this work, seven PhytoPs (PP1-PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization, and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines. Among the tested compounds, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability of MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs displayed significantly enhanced cytotoxic effects on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells. In addition, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells

Apolipoprotein-mediated regulation of lipid metabolism induces distinctive effects in different types of breast cancer cells

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Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development.

INTRODUCTION: Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, the scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established. METHODS: In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model. RESULTS: Our data show that HDL is capable of stimulating migration and can activate signal transduction pathways in the two human breast cancer cell lines, MDA-MB-231 and MCF7. Furthermore, we also show that knockdown of the HDL receptor, SR-BI, attenuates HDL-induced activation of the phosphatidylinositol 3-kinase (PI3K)/protein Kinase B (Akt) pathway in both cell lines. Additional investigations show that inhibition of the PI3K pathway, but not that of the mitogen-activated protein kinase (MAPK) pathway, could lead to a reduction in cellular proliferation in the absence of SR-BI. Importantly, whereas the knockdown of SR-BI led to decreased proliferation and migration in vitro, it also led to a significant reduction in tumor growth in vivo. Most important, we also show that pharmacological inhibition of SR-BI can attenuate signaling and lead to decreased cellular proliferation in vitro. Taken together, our data indicate that both cholesteryl ester entry via HDL-SR-BI and Akt signaling play an essential role in the regulation of cellular proliferation and migration, and, eventually, tumor growth. CONCLUSIONS: These results identify SR-BI as a potential target for the treatment of breast cancer

Development of a Novel High‐Performance Thin Layer Chromatography–Based Method for the Simultaneous Quantification of Clinically Relevant Lipids from Cells and Tissue Extracts

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