Triple negative breast cancer (TNBC) is known to contain a high percentage of CD44(+) /CD24(-/low) cancer stem cells (CSCs), corresponding with a poor prognosis despite systemic chemotherapy. Chloroquine (CQ), an antimalarial drug, is a lysotropic reagent which inhibits autophagy. CQ was identified as a potential CSC inhibitor through in silico gene expression signature analysis of the CD44(+) /CD24(-/low) CSC population. Autophagy plays a critical role in adaptation to stress conditions in cancer cells, and is related with drug resistance and CSC maintenance. Thus, the objectives of this study were to examine the potential enhanced efficacy arising from addition of CQ to standard chemotherapy (paclitaxel) in TNBC and to identify the mechanism by which CQ eliminates CSCs in TNBCs. Herein, we report that CQ sensitizes TNBC cells to paclitaxel through inhibition of autophagy and reduces the CD44(+) /CD24(-/low) CSC population in both preclinical and clinical settings. Also, we are the first to report a mechanism by which CQ regulates the CSCs in TNBC through inhibition of the Janus-activated kinase 2 (Jak2)-signal transducer and activator of transcription 3 signaling pathway by reducing the expression of Jak2 and DNA methyltransferase 1.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138251 | PMC |
| http://dx.doi.org/10.1002/stem.1746 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sertaconazole, an Imidazole Antifungal Agent, Suppresses the Stemness of Breast Cancer Cells by Inhibiting Stat3 Signaling.
In Vivo
December 2024
Graduate Program for Bio-health/Innovative Drug Development using Subtropical Bio-Resources, Jeju National University, Jeju, Republic of Korea;
Background/aim: Breast cancer stem cells (BCSCs) are a subpopulation of tumor cells that play a role in therapeutic resistance. In this study, we demonstrated that sertaconazole, an antifungal agent, displayed a potent inhibition on cancer stem cells (CSCs) and investigated the mechanism of action involved in its anti-BCSC effect.
Materials And Methods: The effect of sertaconazole on BCSCs was investigated using a mammosphere formation assay, a colony formation assay, and a cell migration assay.
Ginsenoside Rg3 attenuates the stemness of breast cancer stem cells by activating the hippo signaling pathway.
Toxicol Appl Pharmacol
January 2025
Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China. Electronic address:
Article Synopsis
- - Ginsenoside Rg3, a compound from ginseng, shows potential in targeting breast cancer stem cells (BCSCs) using a comprehensive approach including network pharmacology and molecular docking analysis.
- - Researchers identified 38 common targets between Rg3 and BCSCs, with key potential targets including Myc, Stat3, and Bcl2, which were validated through molecular docking studies.
- - In vitro experiments demonstrated that Rg3 can induce cell death, suppress growth, and reduce the expression of cancer stem cell markers in BCSCs by activating the Hippo signaling pathway, suggesting it as a promising cancer treatment.
Expression of CD44CD24 cells, SOX2, and STAT3 transcription factors on peripheral blood and tumor tissue of penile squamous cell carcinoma.
J Surg Oncol
September 2024
Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil.
Article Synopsis
- Penile cancer is notably prevalent in underdeveloped countries, and markers like STAT3, CD44, CD24, and SOX2 are being explored for their potential in diagnosing and prognosing this disease.
- A study conducted at the Hospital de Cancer de Pernambuco analyzed blood and tumor tissues of patients from 2015 to 2017, revealing significant differences in the levels of the markers between cancer patients and healthy controls.
- The findings indicated that high levels of CD44, CD24, and low SOX2+ T cells are linked to advanced disease and poor prognosis, while high pSTAT3 and T cell counts were associated with better outcomes in penile cancer patients.
Breast cancer patient-derived organoids for the investigation of patient-specific tumour evolution.
Cancer Cell Int
June 2024
Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, Via G. B. Grassi 74, 20157, Milan, Italy.
Background: A reliable preclinical model of patient-derived organoids (PDOs) was developed in a case study of a 69-year-old woman diagnosed with breast cancer (BC) to investigate the tumour evolution before and after neoadjuvant chemotherapy and surgery. The results were achieved due to the development of PDOs from tissues collected before (O-PRE) and after (O-POST) treatment.
Methods: PDO cultures were characterized by histology, immunohistochemistry (IHC), transmission electron microscopy (TEM), scanning electron microscopy (SEM), confocal microscopy, flow cytometry, real-time PCR, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq) and drug screening.
Blockade of tumor cell-intrinsic PD-L1 signaling enhances AURKA-targeted therapy in triple negative breast cancer.
Front Oncol
May 2024
Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, United States.
Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and mainly affects pre-menopausal and minority women. Because of the lack of ER, PR or HER2 expression in TNBC, there are limited options for tailored therapies. While TNBCs respond initially to standard of care chemotherapy, tumor recurrence commonly occurs within 1 to 3 years post-chemotherapy and is associated with early organ metastasis and a high incidence of mortality.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!