scholarly journals The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

Nutrients ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 581 ◽  
Author(s):  
Ahmed Abdal Dayem ◽  
Hye Choi ◽  
Gwang-Mo Yang ◽  
Kyeongseok Kim ◽  
Subbroto Saha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Anti Cancer

scholarly journals Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2482
Author(s):  
Samson Mathews Samuel ◽  
Elizabeth Varghese ◽  
Lenka Koklesová ◽  
Alena Líšková ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Acquired Resistance ◽  
Breast Cancers ◽  
Intrinsic Resistance ◽  
Mesenchymal Transition ◽  
Cancer Breast

Despite the leaps and bounds in achieving success in the management and treatment of breast cancers through surgery, chemotherapy, and radiotherapy, breast cancer remains the most frequently occurring cancer in women and the most common cause of cancer-related deaths among women. Systemic therapeutic approaches, such as chemotherapy, although beneficial in treating and curing breast cancer subjects with localized breast tumors, tend to fail in metastatic cases of the disease due to (a) an acquired resistance to the chemotherapeutic drug and (b) the development of intrinsic resistance to therapy. The existence of cancer stem cells (CSCs) plays a crucial role in both acquired and intrinsic chemoresistance. CSCs are less abundant than terminally differentiated cancer cells and confer chemoresistance through a unique altered metabolism and capability to evade the immune response system. Furthermore, CSCs possess active DNA repair systems, transporters that support multidrug resistance (MDR), advanced detoxification processes, and the ability to self-renew and differentiate into tumor progenitor cells, thereby supporting cancer invasion, metastasis, and recurrence/relapse. Hence, current research is focusing on targeting CSCs to overcome resistance and improve the efficacy of the treatment and management of breast cancer. Studies revealed that metformin (1, 1-dimethylbiguanide), a widely used anti-hyperglycemic agent, sensitizes tumor response to various chemotherapeutic drugs. Metformin selectively targets CSCs and improves the hypoxic microenvironment, suppresses the tumor metastasis and inflammation, as well as regulates the metabolic programming, induces apoptosis, and reverses epithelial–mesenchymal transition and MDR. Here, we discuss cancer (breast cancer) and chemoresistance, the molecular mechanisms of chemoresistance in breast cancers, and metformin as a chemo-sensitizing/re-sensitizing agent, with a particular focus on breast CSCs as a critical contributing factor to acquired and intrinsic chemoresistance. The review outlines the prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer/chemo-sensitizing drug in the treatment of breast cancer. It intends to provide a rationale for the use of metformin as a combinatory therapy in a clinical setting.

scholarly journals Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1798 ◽  
Author(s):  
Mariarosaria Negri ◽  
Annalisa Gentile ◽  
Cristina de Angelis ◽  
Tatiana Montò ◽  
Roberta Patalano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Vitamin D ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Vitamin D Supplementation

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

scholarly journals Correction: In silico and in vitro studies on the anti-cancer activity of andrographolide targeting survivin in human breast cancer stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247694
Author(s):  
Septelia Inawati Wanandi ◽  
Agus Limanto ◽  
Elvira Yunita ◽  
Resda Akhra Syahrani ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
In Silico ◽  
Human Breast Cancer ◽  
Breast Cancer Stem Cells ◽  
Human Breast ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

2015 ◽  
Vol 112 (45) ◽  
pp. E6215-E6223 ◽  
Author(s):  
Huimin Zhang ◽  
Haiquan Lu ◽  
Lisha Xiang ◽  
John W. Bullen ◽  
Chuanzhao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Cell Phenotype

Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription of the CD47 gene in hypoxic breast cancer cells. Knockdown of HIF activity or CD47 expression increased the phagocytosis of breast cancer cells by bone marrow-derived macrophages. CD47 expression was increased in mammosphere cultures, which are enriched for cancer stem cells, and CD47 deficiency led to cancer stem cell depletion. Analysis of datasets derived from thousands of patients with breast cancer revealed that CD47 expression was correlated with HIF target gene expression and with patient mortality. Thus, CD47 expression contributes to the lethal breast cancer phenotype that is mediated by HIF-1.

Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-κB signaling pathway

2017 ◽  
Vol 57 (3) ◽  
pp. 333-346 ◽  
Author(s):  
Syed S. Islam ◽  
Ibtehaj Al-Sharif ◽  
Ahlam Sultan ◽  
Amer Al-Mazrou ◽  
Adnane Remmal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathway ◽  
Breast Cancer Stem Cells ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Positive Breast Cancer

scholarly journals In silico and in vitro studies on the anti-cancer activity of andrographolide targeting survivin in human breast cancer stem cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240020
Author(s):  
Septelia Inawati Wanandi ◽  
Agus Limanto ◽  
Elvira Yunita ◽  
Resda Akhra Syahrani ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Caspase 3 ◽  
Breast Cancer Stem Cells ◽  
Human Breast ◽  
Caspase 9 ◽  
Anti Cancer ◽  
Apoptotic Activity

Breast cancer stem cells (BCSCs) express high levels of the anti-apoptotic protein, survivin. This study aimed to discover a natural active compound with anti-cancer properties that targeted survivin in human breast cancer stem cells. From the seven examined compounds, andrographolide was selected as a lead compound through in silico molecular docking with survivin, caspase-9, and caspase-3. We found that the affinity between andrographolide and survivin is higher than that with caspase-9 and caspase-3. Human CD24-/CD44+ BCSCs were treated with andrographolide in vitro for 24 hours. The cytotoxic effect of andrographolide on BCSCs was compared to that on human mesenchymal stem cells (MSCs). The expression of survivin, caspase-9, and caspase-3 mRNA was analyzed using qRT-PCR, while Thr34-phosphorylated survivin and total survivin levels were determined using ELISA and Immunoblotting assay. Annexin-V/PI flow cytometry assays were performed to evaluate the apoptotic activity of andrographolide. Our results demonstrate that the CC50 of andrographolide in BCSCs was 0.32mM, whereas there was no cytotoxic effect in MSCs. Moreover, andrographolide decreased survivin and Thr34-phosphorylated survivin, thus inhibiting survivin activation and increasing survivin mRNA in BCSCs. The apoptotic activity of andrographolide was revealed by the increase of caspase-3 mRNA and protein, as well as the increase in both the early and late phases of apoptosis. In conclusion, andrographolide can be considered an anti-cancer compound that targets BCSCs due to its molecular interactions with survivin, caspase-9, and caspase-3, which induce apoptosis. We suggest that the binding of andrographolide to survivin is a critical aspect of the effect of andrographolide.

scholarly journals Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mianmian Liao ◽  
Caiwei Wang ◽  
Bowen Yang ◽  
Danping Huang ◽  
Yifeng Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Specific Marker ◽  
Breast Cscs ◽  
Consolidation Phase ◽  
Regulatory Effects

Accumulating evidence suggests that the root of drug chemoresistance in breast cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely dependent on taxol-promoting autophagy. Our pilot study identified GRP78 as a specific marker for chemoresistance potential of breast CSCs by regulating Wnt/β-catenin signaling. Ai Du Qing (ADQ) is a traditional Chinese medicine formula that has been utilized in the treatment cancer, particularly during the consolidation phase. In the present study, we investigated the regulatory effects and molecular mechanisms of ADQ in promoting autophagy-related breast cancer chemosensitivity. ADQ with taxol decreasing the cell proliferation and colony formation of breast cancer cells, which was accompanied by suppressed breast CSC ratio, limited self-renewal capability, as well as attenuated multi-differentiation. Furthermore, autophagy in ADQ-treated breast CSCs was blocked by taxol via regulation of β-catenin/ABCG2 signaling. We also validated that autophagy suppression and chemosensitizing activity of this formula was GRP78-dependent. In addition, GRP78 overexpression promoted autophagy-inducing chemoresistance in breast cancer cells by stabilizing β-catenin, while ADQ treatment downregulated GRP78, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and consequently attenuated the chemoresistance-promoted effect of GRP78. In addition, both mouse breast cancer xenograft and zebrafish xenotransplantation models demonstrated that ADQ inhibited mammary tumor growth, and the breast CSC subpopulation showed obscure adverse effects. Collectively, this study not only reveals the chemosensitizating mechanism of ADQ in breast CSCs, but also highlights the importance of GRP78 in mediating autophagy-promoting drug resistance via β-catenin/ABCG2 signaling.

scholarly journals Targeting Cancer Stem Cells in Triple-Negative Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 965 ◽  
Author(s):  
Park ◽  
Choi ◽  
Nam
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Therapy Resistance ◽  
Therapeutic Effects ◽  
Self Renewal ◽  
The Future

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks targeted therapy options, and patients diagnosed with TNBC have poorer outcomes than patients with other breast cancer subtypes. Emerging evidence suggests that breast cancer stem cells (BCSCs), which have tumor-initiating potential and possess self-renewal capacity, may be responsible for this poor outcome by promoting therapy resistance, metastasis, and recurrence. TNBC cells have been consistently reported to display cancer stem cell (CSC) signatures at functional, molecular, and transcriptional levels. In recent decades, CSC-targeting strategies have shown therapeutic effects on TNBC in multiple preclinical studies, and some of these strategies are currently being evaluated in clinical trials. Therefore, understanding CSC biology in TNBC has the potential to guide the discovery of novel therapeutic agents in the future. In this review, we focus on the self-renewal signaling pathways (SRSPs) that are aberrantly activated in TNBC cells and discuss the specific signaling components that are involved in the tumor-initiating potential of TNBC cells. Additionally, we describe the molecular mechanisms shared by both TNBC cells and CSCs, including metabolic plasticity, which enables TNBC cells to switch between metabolic pathways according to substrate availability to meet the energetic and biosynthetic demands for rapid growth and survival under harsh conditions. We highlight CSCs as potential key regulators driving the aggressiveness of TNBC. Thus, the manipulation of CSCs in TNBC can be a targeted therapeutic strategy for TNBC in the future.

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