Salinomycin Derivatives Kill Breast Cancer Stem Cells via Lysosomal Iron Targeting.

This study provides highly selective molecules to target the CSC niche, a potential interesting advance for drug development to prevent cancer resistance. PMID: 32083773 [PubMed - as supplied by publisher]
Source: Chemistry - Category: Chemistry Authors: Tags: Chemistry Source Type: research

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AbstractThe mammary gland is a secretory organ, which develops as a network of growing epithelial ducts composed of luminal and basal cells that invade the surrounding adipose tissue through a series of developmental cycles. Mammary stem cells (MaSCs) maintain an accurate tissue homeostasis, and their proliferation and cell fate determination are regulated by multiple hormones and local factors. The WNT pathway plays a critical role in controlling the enormous tissue expansion and remodeling during mammary gland development through the maintenance and differentiation of MaSCs, and its deregulation has been implicated in br...
Source: IUBMB Life - Category: Research Authors: Tags: CRITICAL REVIEW Source Type: research
Abstract In mammary gland development, normal stem cell activity occurs in the embryonic stage and postnatally. Research supports that certain breast cancers contain a small sub-population of cells that mimic stem-like activity. It is believed stem cell activation in the mutated mature human mammary tissue is what drives quiescent epithelial cells to convert to mesenchymal states initiating migration, invasion, and metastasis in breast cancer. The goal of the work reported herein was to investigate early mammary development gene expression in the postnatal pig using fine needle biopsy methods in order to establish...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
In this study, using hormone responsive and hormone independent breast cancer cells, MCF-7 and MDAMB-231 respectively, we studied some of the molecular pathways that contribute to cancer progression. Since the cancer chaperone, Hsp90 inhibitors have entered the clinical trials, we used Hsp90 inhibitor, 17AAG to examine the outcome of altered molecular pathways. The observed differential sensitivity in MCF7 and MDAMB-231 cells to 17AAG treatment is then attributed to both tumor microenvironment mediated by hypoxia and acquired alterations in the endogenous stem cell pool. Interestingly, tumor cells are able to retain epithe...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the main molecules that play an important role in mammary stem cell biology. Mammary stem cells guarantee differentiation of the epithelial mammary cells, the growth of which is regulated by the progesterone-induced RANKL signaling pathway. The crosstalk between progesterone receptor, stimulated by progesterone and its a...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
ConclusionsWe identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, reflecting a better patient prognosis. Thus, the identified gene panel may be of interest for the clinical management of patients with aggressive TNBC.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
Abstract Breast cancer, an intricate and highly heterogeneous disorder, has presently afflicted 2.09 million females globally. Nonetheless, chemoresistance remains a paramount challenge in the treatment of breast cancer. Owing to its assorted nature, the chemoresistant mechanisms of breast cancer still need intensive research. The presently available interventions are inadequate to target chemoresistance, therefore more efficient alternatives are urgently needed to improvise existing therapeutic regimens. A myriad of strategies is being explored, such as cancer stem cells (CSCs), immunotherapy, gene therapy, miRNA...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research
Publication date: Available online 9 January 2020Source: Stem Cell ReportsAuthor(s): Raghava R. Sunkara, Rahul M. Sarate, Priyanka Setia, Sanket Shah, Sanjay Gupta, Pankaj Chaturvedi, Poonam Gera, Sanjeev K. WaghmareSummaryWnt signaling is involved in the regulation of cancer stem cells (CSCs); however, the molecular mechanism involved is still obscure. SFRP1, a Wnt inhibitor, is downregulated in various human cancers; however, its role in tumor initiation and CSC regulation remains unexplored. Here, we used a skin carcinogenesis model, which showed early tumor initiation in Sfrp1−/− (Sfrp1 knockout) mice and i...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Abstract Cancer stem cell like cells (CSCs) present a challenge in the management of cancers due to their involvement in the development of resistance against various chemotherapeutic agents. Over expression of ABCG2 transporter gene is one of the factors responsible for drug resistance in CSCs, which causes efflux of therapeutic drugs from these cells. The development of inhibitors against CSCs has not achieved any significant success, till date. In this work, we have evaluated the anti-proliferative activity of curcumin (Cur) and quinacrine (QC) against CSCs using in vitro model system. Cur and QC synergisticall...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
Authors: Al-Othman N, Alhendi A, Ihbaisha M, Barahmeh M, Alqaraleh M, Al-Momany BZ Abstract Breast cancer (BC) is among the most prevalent type of malignancy affecting females worldwide. BC is classified into different types according to the status of the expression of receptors such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and progesterone receptor (PR). Androgen receptor (AR) appears to be a promising therapeutic target of breast cancer. Binding of 5α-dihydrotestosterone (DHT) to AR controls the expression of microRNA (miRNA) molecules in BC, consequently, affecting protei...
Source: Breast Disease - Category: Cancer & Oncology Tags: Breast Dis Source Type: research
The ∆Np63 isoform of the p53‐family transcription factor Trp63 is a key regulator of mammary epithelial stem cells that is involved in breast cancer development. To investigate the role of ∆Np63 at different stages of normal mammary gland development, we generated a ∆Np63‐inducible conditional knockout (cKO) mouse model. We demonstrate that the deletion of ∆Np63 at puberty results in depletion of mammary stem cell‐enriched basal cells, reduces expression of E‐cadherin and β‐catenin, and leads to a closed ductal lumen. RNA‐sequencing analysis reveals reduced expression of oxid ative phosphoryla...
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research
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