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

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.

2018 ◽  
Vol 19 (12) ◽  
pp. 3813 ◽  
Author(s):  
Dong Kim ◽  
Je-Yoel Cho

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.


Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3128
Author(s):  
Jong Woo Park ◽  
Jee Hun Park ◽  
Jeung-Whan Han

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.


Author(s):  
Dong Wook Kim ◽  
Je-Yoel Cho

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.


2019 ◽  
Vol 14 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Gabriele D. Bigoni-Ordóñez ◽  
Daniel Czarnowski ◽  
Tyler Parsons ◽  
Gerard J. Madlambayan ◽  
Luis G. Villa-Diaz

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.


2017 ◽  
Vol 46 (38) ◽  
pp. 12785-12789 ◽  
Author(s):  
C. Lu ◽  
K. Laws ◽  
A. Eskandari ◽  
K. Suntharalingam

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.


2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat

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.


2020 ◽  
Vol 49 (14) ◽  
pp. 4211-4215
Author(s):  
Arvin Eskandari ◽  
Arunangshu Kundu ◽  
Alice Johnson ◽  
Sanjib Karmakar ◽  
Sushobhan Ghosh ◽  
...  

A multi-nuclear, triangular-shaped palladium(ii) complex is shown to equipotently kill bulk cancer cells and cancer stem cells (CSCs) in the micromolar range.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sheetal Dyall ◽  
Simon A. Gayther ◽  
Dimitra Dafou

The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs), or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.


RSC Advances ◽  
2016 ◽  
Vol 6 (106) ◽  
pp. 104763-104781 ◽  
Author(s):  
Aleksandra Božić ◽  
Aleksandar Marinković ◽  
Snežana Bjelogrlić ◽  
Tamara R. Todorović ◽  
Ilija N. Cvijetić ◽  
...  

Study of antitumor activity of mono- and bis-quinoline based (thio)carbohydrazones on THP-1 and AsPC-1 cancer stem cells, revealed that thiocarbohydrazones had superior pro-apoptotic activity than carbohydrazones with multi-target profile activities.


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