Cancer Stem Cells and Multi-drug Resistance by Flow Cytometry

2017 ◽  
pp. 253-266
Author(s):  
Jordi Petriz
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Multi Drug Resistance

scholarly journals Isolation of cancer stem cells by selection for miR-302 expressing cells

2018 ◽  
Author(s):  
Karim Rahimi ◽  
Annette C. Füchtbauer ◽  
Fardin Fathi ◽  
Seyed Javad Mowla ◽  
Ernst-Martin Füchtbauer
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Host Gene ◽  
Multi Drug Resistance ◽  
Term Therapy ◽  
Specific Gene ◽  
Specific Marker

AbstractCancer stem cells receive increasing interest because they are believed to be a major reason for long-term therapy failure. The reason for the therapy resistance of cancer stem cells lies partially in their multi-drug resistance and partially in the ability to rest mitotically inactive in the hypoxic center of tumors. Due to their variable number and their often low proliferation rate, cancer stem cells are difficult to purify in decent quantities and to grow in cell culture systems, where they are easily outcompeted by faster growing more ‘differentiated’, i.e. less stem cell-like tumor cells. Here we present a proof of principle study based on the idea to select cancer stem cells by means of the expression of a stem cell-specific gene. We inserted a selectable egfp-neo coding sequence in the last exon of the non-coding murine miR-302 host gene. As a stem cell specific regulatory element, we used 2.1 kb of the genomic region immediately upstream of the miR-302 host gene transcription start. Stable transgenic CJ7 embryonic stem cells were used to induce teratomas. After three weeks, tumors were removed for analysis and primary cultures were established. Stem-like cells were selected from these culture based on G418 selection. When the selection was removed, stem cell morphology and miR-302 expression were rapidly lost, indicating that it were not the original ES cells that have been isolated. In conclusion, we show the possibility to use drug resistance expressed from a regulatory sequence of a stem cell-specific marker, to isolate and propagate cancer stem cells that otherwise might be hidden in the majority of tumor cells.

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

scholarly journals Repositioning Trimebutine Maleate as a Cancer Treatment Targeting Ovarian Cancer Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 918
Author(s):  
Heejin Lee ◽  
Oh-Bin Kwon ◽  
Jae-Eon Lee ◽  
Yong-Hyun Jeon ◽  
Dong-Seok Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Ovarian Cancer Cells ◽  
Therapeutic Drug ◽  
G1 Arrest ◽  
Dead Cell ◽  
Trimebutine Maleate ◽  
Simultaneous Inhibition

The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. This study evaluated the effect of trimebutine maleate (TM) targeting ovarian CSCs, using A2780-SP cells acquired by a sphere culture of A2780 epithelial ovarian cancer cells. TM is indicated as a gastrointestinal motility modulator and is known to as a peripheral opioid receptor agonist and a blocker for various channels. The GI50 of TM was approximately 0.4 µM in A2780-SP cells but over 100 µM in A2780 cells, demonstrating CSCs specific growth inhibition. TM induced G0/G1 arrest and increased the AV+/PI+ dead cell population in the A2780-SP samples. Furthermore, TM treatment significantly reduced tumor growth in A2780-SP xenograft mice. Voltage gated calcium channels (VGCC) and calcium-activated potassium channels (BKCa) were overexpressed on ovarian CSCs and targeted by TM; inhibition of both channels reduced A2780-SP cells viability. TM reduced stemness-related protein expression; this tendency was reproduced by the simultaneous inhibition of VGCC and BKCa compared to single channel inhibition. In addition, TM suppressed the Wnt/β-catenin, Notch, and Hedgehog pathways which contribute to many CSCs characteristics. Specifically, further suppression of the Wnt/β-catenin pathway by simultaneous inhibition of BKCa and VGCC is necessary for the effective and selective action of TM. Taken together, TM is a potential therapeutic drug for preventing ovarian cancer recurrence and drug resistance.

The impact of fusion genes on cancer stem cells and drug resistance

2021 ◽  
Author(s):  
Saurav Panicker ◽  
Sivaramakrishnan Venkatabalasubramanian ◽  
Surajit Pathak ◽  
Satish Ramalingam
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Fusion Genes ◽  
The Impact

Natural products targeting cancer stem cells: a revisit

2021 ◽  
Vol 28 ◽  
Author(s):  
Jiahua Cui ◽  
Jiajun Qian ◽  
Larry Ming-Cheung Chow ◽  
Jinping Jia
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Biologically Active ◽  
Cellular Targets ◽  
Drug Candidates ◽  
Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

scholarly journals Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lijuan Zou ◽  
Hengpeng He ◽  
Zhiguo Li ◽  
Ou Chen ◽  
Xiukun Jia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Noncoding Rna ◽  
Cell Subset ◽  
Luciferase Reporter ◽  
Stem Cell Markers ◽  
Self Renewal

AbstractLong noncoding RNAs (lncRNAs) are implicated tumor development in a range of different cancers, including pancreatic cancer (PC). Cancer stem cells (CSCs), a drug-resistant cancer cell subset, drive tumor progression in PC. In this work, we aimed to investigate the mechanism by which lncRNA LINC00261 affects the biological functions of CSCs during the progression of PC. Microarray analysis of differentially expressed genes and lncRNAs suggested that LINC00261 is downregulated in PC. Both LINC00261 and ITIH5 were confirmed to be downregulated in PC cells and PC stem cells. Gain-of-function and loss-of-function investigations were performed to analyze their effects on cell proliferation, drug resistance, cell cycle distribution, self-renewal, invasion, and ultimately overall tumorigenicity. These experiments revealed that the expression of stem cell markers was reduced, and cell proliferation, self-renewal ability, cell invasion, drug resistance, and tumorigenicity were all suppressed by upregulation of LINC00261 or ITIH5. The results of dual-luciferase reporter gene, ChIP, and RIP assays indicated that LINC00261 binds directly to GATA6, increasing its activity at the ITIH5 promoter. The presence of LINC00261 and GATA6 inhibited the self-renewal and tumorigenesis of PC stem cells, while silence of ITIH5 rescued those functions. Collectively, this study identifies the tumor suppressive activity of LINC00261 in PC, showing that this lncRNA limits the functions of PC stem through an ITIH5/GATA6 regulatory pathway.

Colon cancer: Cancer stem cells markers, drug resistance and treatment

2014 ◽  
Vol 68 (8) ◽  
pp. 911-916 ◽  
Author(s):  
Zuzana Kozovska ◽  
Veronika Gabrisova ◽  
Lucia Kucerova
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Stem Cells
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