A2B adenosine receptor agonist induces cell cycle arrest and apoptosis in breast cancer stem cells via ERK1/2 phosphorylation

2017 ◽  
Vol 41 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Seyyed Mehdi Jafari ◽  
Hamid Reza Joshaghani ◽  
Mojtaba Panjehpour ◽  
Mahmoud Aghaei
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Adenosine Receptor ◽  
Receptor Agonist ◽  
Breast Cancer Stem Cells ◽  
Cycle Arrest ◽  
Adenosine Receptor Agonist

A3 Adenosine Receptor Agonist Inhibited Survival of Breast Cancer Stem Cells via GLI-1 and ERK1/2 Pathway

2017 ◽  
Vol 118 (9) ◽  
pp. 2909-2920 ◽  
Author(s):  
Seyyed Mehdi Jafari ◽  
Mojtaba Panjehpour ◽  
Mahmoud Aghaei ◽  
Hamid Reza Joshaghani ◽  
Seyed Ehsan Enderami
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Adenosine Receptor ◽  
Receptor Agonist ◽  
Breast Cancer Stem Cells ◽  
Adenosine Receptor Agonist ◽  
A3 Adenosine Receptor ◽  
Gli 1

Cell cycle arrest and apoptogenic properties of opium alkaloids noscapine and papaverine on breast cancer stem cells

2015 ◽  
Vol 25 (5) ◽  
pp. 388-395 ◽  
Author(s):  
Saharolsadat Sajadian ◽  
Melody Vatankhah ◽  
Maryam Majdzadeh ◽  
Shide Montaser Kouhsari ◽  
Mohammad Hossein Ghahremani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Breast Cancer Stem Cells ◽  
Opium Alkaloids ◽  
Cycle Arrest

scholarly journals PAWI-2 overcomes tumor stemness and drug resistance via cell cycle arrest in integrin β3-KRAS-dependent pancreatic cancer stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiongjia Cheng ◽  
John R. Cashman
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Specific Inhibitor ◽  
Feedback Mechanism ◽  
Major Health Problem ◽  
Cycle Arrest ◽  
Drug Inhibition

Abstract Today, pancreatic cancer (PC) remains a major health problem in the US. The fact that cancer stem cells (CSCs) become enriched in humans following anti-cancer therapy implicates CSCs as key contributors to tumor dormancy, metastasis, and relapse in PC. A highly validated CSC model (FGβ3 cells) was used to test a novel compound (PAWI-2) to eradicate CSCs. Compared to parental bulk FG cells, PAWI-2 showed greater potency to inhibit cell viability and self-renewal capacity of FGβ3 cells. For FGβ3 cells, dysregulated integrin β3-KRAS signaling drives tumor progression. PAWI-2 inhibited β3-KRAS signaling independent of KRAS. This is clinically relevant. PAWI-2 targeted the downstream TBK1 phosphorylation cascade that was negatively regulated by optineurin phosphorylation via a feedback mechanism. This was confirmed by TBK1 genetic knockdown or co-treatment with TBK1-specific inhibitor (MRT67307). PAWI-2 also overcame erlotinib (an EGFR inhibitor) resistance in FGβ3 cells more potently than bortezomib. In the proposed working model, optineurin acts as a key regulator to link inhibition of KRAS signaling and cell cycle arrest (G2/M). The findings show PAWI-2 is a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.

scholarly journals Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

2014 ◽  
Vol 34 (5) ◽  
pp. 1249-1256 ◽  
Author(s):  
BURAK CEM SONER ◽  
HUSEYIN AKTUG ◽  
EDA ACIKGOZ ◽  
FAHRIYE DUZAGAC ◽  
UMMU GUVEN ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Prostate Cancer Stem Cells

scholarly journals Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3233 ◽  
Author(s):  
Ying Zhu ◽  
Li-Yun Shi ◽  
Yan-Min Lei ◽  
Yan-Hong Bao ◽  
Zhao-Yang Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Laryngeal Cancer ◽  
Signal Pathway ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Radio Sensitivity

BackgroundTreatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells.MethodTo investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3pin vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p.ResultOverexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity.ConclusionIn the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers.

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 Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44+and CD24−breast cancer stem cells

2017 ◽  
Vol 50 (4) ◽  
pp. e12345 ◽  
Author(s):  
S.M. Jafari ◽  
H.R. Joshaghani ◽  
M. Panjehpour ◽  
M. Aghaei ◽  
N. Zargar Balajam
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Regulatory Effects ◽  
Gli 1
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