scholarly journals Fermented Ginseng Extract, BST204, Suppresses Tumorigenesis and Migration of Embryonic Carcinoma through Inhibition of Cancer Stem Cell Properties

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3128
Author(s):  
Jong Woo Park ◽  
Jee Hun Park ◽  
Jeung-Whan Han
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Tumor Cell ◽  
Ginseng Extract ◽  
Embryonic Carcinoma ◽  
Fermented Ginseng

The pharmacological effects of BST204—a fermented ginseng extract—on several types of cancers have been reported. However, the effects of ginseng products or single ginsenosides against cancer stem cells are still poorly understood. In this study, we identified the anti-tumorigenic and anti-invasive activities of BST204 through the suppression of the cancer stem cell marker, CD133. The treatment of embryonic carcinoma cells with BST204 induced the expression of the tumor suppressor protein, p53, which decreased the expression of cell cycle regulatory proteins and downregulated the expression of CD133 and several stemness transcription factors. These changes resulted in both the inhibition of tumor cell proliferation and tumorigenesis. The knockdown of CD133 suggests that it has a role in tumorigenesis, but not in cancer cell proliferation or cell cycle arrest. Treatment with BST204 resulted in the reduced expression of the mesenchymal marker, N-cadherin, and the increased expression of the epithelial marker, E-cadherin, leading to the suppression of tumor cell migration and invasion. The knockdown of CD133 also exhibited an anti-invasive effect, indicating the role of CD133 in tumor invasion. The single ginsenosides Rg3 and Rh2—major components of BST204—exhibited limited effects against cancer stem cells compared to BST204, suggesting possible synergism among several ginsenoside compounds.

scholarly journals NQO1 is Required for β-Lapachone-Mediated Downregulation of Breast-Cancer Stem-Cell Activity

2018 ◽  
Vol 19 (12) ◽  
pp. 3813 ◽  
Author(s):  
Dong Kim ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Breast Cancer Stem Cell ◽  
Cancer Development ◽  
Dependent Manner ◽  
Mammosphere Formation

Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. The β-lapachone (bL) compound is widely used to treat cancer development; however, its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast-cancer stem-cell (BCSC) marker-positive cells, MDA-MB-231. MDA-MB-231 cells, which are negative for reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase (NQO1) expression, were constructed to stably express NQO1 (NQO1 stable cells). The effect of bL on these cells was evaluated by wound healing and Transwell cell-culture chambers, ALDEFLUOR assay, and mammosphere formation assay. Here, we show that bL inhibited the proliferative ability of mammospheres derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. The bL treatment efficiently downregulated the expression level of BCSC markers cluster of differentiation 44 (CD44), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and discs large (DLG)-associated protein 5 (DLGAP5) that was recently identified as a stem-cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulated cell proliferation and migration activities. These results strongly suggest that bL could be a therapeutic agent for targeting breast-cancer stem-cells with proper NQO1 expression.

scholarly journals Effect of CD44 knockdown on the biological characteristics of breast cancer stem cells

2020 ◽  
Author(s):  
Zi Lei ◽  
Yang-Li Hu ◽  
Qiang Feng ◽  
Li Wang ◽  
Xin-Yan Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Biological Characteristics ◽  
Breast Cancer Stem Cells ◽  
Transcript Variants

Abstract Background: CD44 is an important surface marker of breast cancer stem cells (BCSCs), but it is unclear whether it is involved in the stemness of BCSCs. This has limited the development of new therapeutic strategies for breast cancer. Previous studies have shown that many CD44 variants generated through alternative splicing are involved in the development of breast cancer, but their exact role in BCSCs remains unclear. Therefore, we analyzed the CD44 transcript variants in BCSCs derived from the MDA-MB-435 cell line, and aimed to investigate whether CD44s knockdown could affect the biological characteristics of BCSCs.Methods: CD44+/CD24- cells were isolated among the MDA-MB-435 cells by flow cytometry, and the CD44 transcript variants were detected by RT-PCR in CD44+/CD24- cells. Due to the high expression of CD44 standard splice isoform (CD44s) in CD44+/CD24- cells, CD44s knockdown was generated using small hairpin RNA (shRNA). The effects of CD44s knockdown on the biological characteristics of BCSCs was detected using cell proliferation assay, colony formation assay, cell cycle and apoptosis assay, tumor sphere formation assay, would-healing assay, and Matrigel invasion assay. Tumorigenesis of the CD44+/CD24- cells with CD44s knockdown was investigated in vivo with NOD/SCID mice. The expression of cancer stem cell stemness-related genes, such as Bcl-2, CCNE2, EGFR, MMP7, Muc1, and Myc was also detected by qPCR.Results: Our results revealed that the mRNA expression of CD44 transcript variants was heterogeneous, and CD44s is highly expressed in BCSCs. CD44s depletion inhibited the proliferation, made cell cycle stay in G0/G1 phase, promoted the apoptosis and necrosis of BCSCs, inhibited the ability of self-renewal and invasion along with the expression of cancer stem cell-related genes in BCSCs. Moreover, CD44s knockdown inhibited the tumorigenesis ability in vivo.Conclusion: Our findings revealed that CD44s is the predominant isoform expressed in BCSCs, and is an important molecule for maintaining the properties of BCSCs. Targeting CD44s in BCSCs may be a potential new direction for breast cancer treatment.

scholarly journals NQO1 is Required for Beta-lapachone-mediated Downregulation of Breast Cancer Stem Cell Activity

2018 ◽  
Author(s):  
Dong Wook Kim ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Breast Cancer Stem Cell ◽  
Cancer Development ◽  
Proliferative Potential ◽  
Dependent Manner

Background: Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. beta-lapachone (bL) has been widely used to treat cancer development, but its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast cancer stem cell (BCSC) marker positive cells, MDA-MB-231. Methods: MDA-MB-231 Cells, which is negative for NQO1 expression, was constructed to stably express NQO1(NQO1 stable cells) to see the effect of bL. The effect of bL on cells were evaluated by wound healing and Transwell cell culture chambers, and ALDEFLUOR assay. Results: Here, we show that bL inhibited the proliferative ability of mammosphere derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. bL treatment efficiently downregulated expression level of BCSC markers CD44, ALDH1A1, and DLGAP5 that recently identified as a stem cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulates cell proliferation and migration activities. Conclusions: These results strongly suggest that bL could be a therapeutic agent targeting breast cancer stem cells with proper NQO1 expression.

scholarly journals The Role of Serotonin in Breast Cancer Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3171
Author(s):  
William D. Gwynne ◽  
Mirza S. Shakeel ◽  
Adele Girgis-Gabardo ◽  
John A. Hassell
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Tumor Cell ◽  
Breast Tumors ◽  
Breast Cancer Stem Cells ◽  
Selective Antagonists

Breast tumors were the first tumors of epithelial origin shown to follow the cancer stem cell model. The model proposes that cancer stem cells are uniquely endowed with tumorigenic capacity and that their aberrant differentiation yields non-tumorigenic progeny, which constitute the bulk of the tumor cell population. Breast cancer stem cells resist therapies and seed metastases; thus, they account for breast cancer recurrence. Hence, targeting these cells is essential to achieve durable breast cancer remissions. We identified compounds including selective antagonists of multiple serotonergic system pathway components required for serotonin biosynthesis, transport, activity via multiple 5-HT receptors (5-HTRs), and catabolism that reduce the viability of breast cancer stem cells of both mouse and human origin using multiple orthologous assays. The molecular targets of the selective antagonists are expressed in breast tumors and breast cancer cell lines, which also produce serotonin, implying that it plays a required functional role in these cells. The selective antagonists act synergistically with chemotherapy to shrink mouse mammary tumors and human breast tumor xenografts primarily by inducing programmed tumor cell death. We hypothesize those serotonergic proteins of diverse activity function by common signaling pathways to maintain cancer stem cell viability. Here, we summarize our recent findings and the relevant literature regarding the role of serotonin in breast cancer.

PS02.060: EXPLORATION OF RADIOSENSITIVITY-RELATED LNCRNA IN ESOPHAGEAL CANCER STEM CELL

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 137-138
Author(s):  
Jiancheng Li ◽  
Weijie Sun
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Expression Level ◽  
Adherent Cells ◽  
Realtime Pcr ◽  
Tumor Sphere

Abstract Background Esophageal cancer stem cells are the most radiation-resistant cells, to study radiosensitivity with esophageal cancer stem cells is a better method, Previously study was only the relevant microRNA research, so we explore radiosensitivity-related LncRNA in esophageal cancer stem cell. Methods The Eca109 cells were divided into tumor sphere cells group and adherent cells group by using suspended and adherent culture. Differences in stem cell characteristics of two groups were compared by CD44 positive expression rate, CCK8 cell proliferation and plate cloning formation. Using Arraystar LncRNA microarray analysis the gene expression differences of CD44+ esophageal cancer stem cells and CD44− esophageal cancer cells sorting out by flow separation technology. Bioinformatics analysis and real-time PCR were applied to verified the specific LncRNA related to radiation sensitivity of esophageal cancer stem cells. Results 1.The result of CCK8 cell proliferation experience showed that the absorbance value of the tumor sphere cells group was significantly higher than and adherent cells group after 24h, 48h and 72h (P < 0.05). The cell clone formation rate of the tumor sphere cells group was higher than adherent cells group (P < 0.05). 2. The plate cloning formation showed that the values of D0, Dq, N and SF2 were significantly higher in the tumor sphere cells group than adherent cells group, and the radiation sensitization ratio was 1.556. 3. Arraystar LncRNA chip analysis showed following the criteria that DEGseq at |log2Ratio| ≥ 1和q < 0.05, 4961 DEGs including 2517 up-regualted genes and 2444 down-regulated genes were identified. 4. We verified the top 10 difference LncRNA genes by realtime PCR. The results showed that MSTRG. 73,085 was down-regulated and its expression level on average was 20.7 times (chip was 49.3 times), CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated and their expression level on average were 2.7, 8.7, 3.7, 5, 7 (chip were 8.2, 5.2, 78.9, 3, 4.7 times). Conclusion We verified the different LncRNA genes by arraystar LncRNA chip and realtime PCR, The results showed that MSTRG. 73,085 was down-regulated and CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated. These LncRNA genes may be related to the radiosensitivity of esophageal cancer stem cells and could be a potential new target for esophageal squamous carcinoma. Disclosure All authors have declared no conflicts of interest.

Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells

2019 ◽  
Vol 14 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Gabriele D. Bigoni-Ordóñez ◽  
Daniel Czarnowski ◽  
Tyler Parsons ◽  
Gerard J. Madlambayan ◽  
Luis G. Villa-Diaz
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
The Self ◽  
Self Renewal ◽  
Terminal Disease

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin &#945;6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

scholarly journals Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan Moore ◽  
Stephen Lyle
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Slow Cycling ◽  
Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

scholarly journals The evolving concept of cancer and metastasis stem cells

2012 ◽  
Vol 198 (3) ◽  
pp. 281-293 ◽  
Author(s):  
Irène Baccelli ◽  
Andreas Trumpp
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Cell ◽  
Dynamic Processes ◽  
Cellular Composition ◽  
Tumor Mass ◽  
Tumor Relapse ◽  
Cancerous Cells ◽  
Heterogeneous Tumor

The cancer stem cell (CSC) concept, which arose more than a decade ago, proposed that tumor growth is sustained by a subpopulation of highly malignant cancerous cells. These cells, termed CSCs, comprise the top of the tumor cell hierarchy and have been isolated from many leukemias and solid tumors. Recent work has discovered that this hierarchy is embedded within a genetically heterogeneous tumor, in which various related but distinct subclones compete within the tumor mass. Thus, genetically distinct CSCs exist on top of each subclone, revealing a highly complex cellular composition of tumors. The CSC concept has therefore evolved to better model the complex and highly dynamic processes of tumorigenesis, tumor relapse, and metastasis.

scholarly journals A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster

2017 ◽  
Vol 46 (38) ◽  
pp. 12785-12789 ◽  
Author(s):  
C. Lu ◽  
K. Laws ◽  
A. Eskandari ◽  
K. Suntharalingam
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Schiff Base ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Cyclooxygenase 2 ◽  
Oxygen Species

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties,1–4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency.

scholarly journals Understanding the Influence of Substrate When Growing Tumorspheres

2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Stem Cell Niche ◽  
Cell Number ◽  
Hard Substrate ◽  
Cell Niche

Abstract Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. A specific condition for the growth of the cancer stem cell number is also obtained.

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