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Natural agents are increasingly studied to augment conventional treatment, and garlic (Allium sativum) shows anti-cancer activity by affecting proliferation, motility, and malignant progression. This study evaluates garlic extract effects on TNBC cell lines, revealing subtype-dependent changes in morphology, cell cycle, and invasion linked to Akt signaling down-modulation. 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Subtype-Dependent Down-Modulation of Akt Signaling  \nFederica Brugnoli 1, Marcello Dell’Aira 1, Paola Tedeschi 2, Silvia Grassilli 3, *, Marina Pierantoni 1, Rebecca Foschi 1 and Valeria Bertagnolo 1, *  \nCitation: Brugnoli, F.; Dell’Aira, M.; Tedeschi, P.; Grassilli, S.; Pierantoni, M.; Foschi, R.; Bertagnolo, V. Effects of Garlic on Breast Tumor Cells with a Triple Negative Phenotype: Peculiar Subtype-Dependent Down  \n-Modulation of Akt Signaling. Cells 2024, 13, 822. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells13100822](10.3390/cells13100822)  \nAcademic Editor: Ceshi Chen  \nReceived: 29 March 2024  \nRevised: 30 April 2024  \nAccepted: 9 May 2024  \nPublished: 11 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; bgf@unife.it (F.B.); [marcello.dellaira@unife.it](marcello.dellaira@unife.it) (M.D.); [marina.pierantoni@unife.it](marina.pierantoni@unife.it) (M.P.); [rebecca.foschi@unife.it](rebecca.foschi@unife.it) (R.F.)  \n2 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara,  \n44121 Ferrara, Italy; [tdspla@unife.it](tdspla@unife.it)  \n3 Department of Environmental Sciences and Prevention and LTTA Centre, University of Ferrara,  \n44121 Ferrara, Italy  \n* Correspondence: [grsslv@unife.it](grsslv@unife.it) (S.G.); [bgv@unife.it](bgv@unife.it) (V.B.); Tel.: +39-0532-455939 (V.B.)  \nAbstract: Breast cancer includes tumor subgroups with morphological, molecular, and clinical differences. Intrinsic heterogeneity especially characterizes breast tumors with a triple negative phenotype, often leading to the failure of even the most advanced therapeutic strategies. To improve breast cancer treatment, the use of natural agents to integrate conventional therapies is the subject of ever-increasing attention. In this context, garlic (Allium sativum) shows anti-cancerous potential, interfering with the proliferation, motility, and malignant progression of both non-invasive and invasive breast tumor cells. As heterogeneity could be at the basis of variable effects, the main objective of our study was to evaluate the anti-tumoral activity of a garlic extract in breast cancer cells with a triple negative phenotype. Established triple negative breast cancer (TNBC) cell lines from patient-derived xenografts (PDXs) were used, revealing subtype-dependent effects on morphology, cell cycle, and invasive potential, correlated with the peculiar down-modulation of Akt signaling, a crucial regulator in solid tumors. Our results first demonstrate that the effects of garlic on TNBC breast cancer are not unique and suggest that only more precise knowledge of the mechanisms activated by this natural compound in each tumor will allow for the inclusion of garlic in personalized therapeutic approaches to breast cancer.  \nKeywords: breast cancer; garlic extract; Akt; TNBC subtypes; PDX-derived cells.  \n1. Introduction  \nBreast cancer (BC) is the most diagnosed tumor and the leading cause of cancer-related deaths in women worldwide [1] . BC is a highly heterogenous disease, showing differences in morphology, prognosis, and response to therapy, based on both histopathological and molecular characteristics [2–4] . BC classification is primarily based on the expression levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), allowing us to identify groups of breast tumors with distinct characteristics in terms of proliferation, mutated genes, and invasi","cbCaitYWfp6MRTfK","https://ap.wps.com/l/cbCaitYWfp6MRTfK","pdf",7690900,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"Why is heterogeneity important in triple negative breast cancer (TNBC)?\",\"answer\":\"TNBC shows intrinsic heterogeneity that contributes to variable responses and therapeutic failure, even when using advanced treatment strategies.\"},{\"question\":\"What is the main objective of the study on garlic?\",\"answer\":\"To assess the anti-tumoral activity of a garlic extract in breast cancer cells with a triple negative phenotype, focusing on subtype-dependent effects.\"},{\"question\":\"How does the study link garlic effects to Akt signaling?\",\"answer\":\"The observed subtype-dependent outcomes in morphology, cell cycle, and invasive potential correlate with down-modulation of Akt signaling, described as a crucial regulator in solid tumors.\"}]","Effects of Garlic on Breast Tumor Cells with a Triple Negative Phenotype: Peculiar Subtype-Dependent Down-Modulation of Akt Signaling - Research Abstract | PDF",1789978091,48]