scholarly journals The combination therapy of salinomycin and gefitinib using poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells

2017 ◽  
Vol Volume 10 ◽  
pp. 5653-5666 ◽  
Author(s):  
Yu Zhang ◽  
Qi Zhang ◽  
Jing Sun ◽  
Huijie Liu ◽  
Qingfeng Li
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Combination Therapy ◽  
Ethylene Glycol ◽  
Cancer Cells ◽  
Glycolic Acid ◽  
Poly Ethylene Glycol ◽  
Lung Cancer Stem Cells ◽  
Poly Ethylene

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways

2019 ◽  
Author(s):  
FanPing Wang ◽  
Jiateng Zhong ◽  
Shanshan Wang ◽  
Caijuan Qiao ◽  
Xiangyang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Background: Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. Methods: Lung cancer stem cells (CD133-positive cells) were isolated by MACs and then measured by flow cytometry. The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The expressions of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) in cells were measured by quantitative reverse transcription polymerase chain reaction (qPCR) and western blot assays. The expression of transcription factor SOX2 in lung cancer stem cells was also determined by western blot assay. Shh was knocked down by siRNA to further study the role of SFN and Shh signaling pathways in lung cancer. Results: SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously. Meanwhile, we observed that Sonic Hedgehog (SHH) signaling pathway, SOX2 and Polyhomeotic Homolog 3 (PHC3) were highly activated in lung cancer stem cells. Knock-down of Shh led to reduced H460 and A549 cells proliferation. Furthermore, we observed that SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells. In addition, SFN combined with Knock-down of Shh gene showed a greater effect on the proliferation of lung cancer cells. Conclusion: SFN is an effective new drug which can inhibit proliferation of lung cancer stem cells through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung cancer stem cells.

scholarly journals Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fanping Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Lung Cancer Cells ◽  
Sonic Hedgehog Signaling ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

AbstractSulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.

A Novel Peptidomimetic Therapeutic for Selective Suppression of Lung Cancer Stem Cells Over Non-stem Cancer Cells

2021 ◽  
pp. 105340
Author(s):  
Satya Prakash Shukla ◽  
Aaron Raymond ◽  
Vineeta Rustagi ◽  
Samanth R. Kedika ◽  
Olivia Tran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Selective Suppression ◽  
Lung Cancer Stem Cells

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Sonic Hedgehog Signaling Pathway and Polyhomeotic Homolog3

2021 ◽  
Author(s):  
FanPing Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells (CSCs). CD133-positive lung cancer cells were isolated by MACs from lung cancer A549 and H460 cells. And then, the expression of CD133 was measured by flow cytometry assays (FACS). The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The mRNA expression of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) was measured by quantitative reverse transcription polymerase chain reaction (QPCR). And the protein expression of Shh, Smo, Gli1 and PHC3 was determined by western blotting. Shh was knocked down by siRNA to further study the role of Shh signaling pathways in lung CSCs. SFN inhibited the proliferation of lung cancer cells and lung CSCs simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in A549 /CD133+ and H460 /CD133+ cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of A549/ CD133+ and H460/ CD133+ cells, and decreased the protein expression of PHC3 in A549/ CD133+ and H460/ CD133+ cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in A549/ CD133+ and H460/ CD133+ cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-shh cells is weaker than that of siRNA-control cells. SFN is an effective new drug which can inhibit proliferation of lung CSCs through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung CSCs.

scholarly journals Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

2021 ◽  
Vol 14 (11) ◽  
pp. 1169
Author(s):  
Hussein Hamad ◽  
Birgitte Brinkmann Olsen
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cell Death ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Development Of Resistance ◽  
Human Lung Cancer Cells ◽  
Lung Cancer Stem Cells

Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells. Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells. We found that CBD decreased viability and induced cell death in both cell populations. Furthermore, we found that CBD activated the effector caspases 3/7, increased the expression of pro-apoptotic proteins, increased the levels of reactive oxygen species, as well as a leading to a loss of mitochondrial membrane potential in both populations. We also found that CBD decreased self-renewal, a hallmark of cancer stem cells. Overall, our results suggest that CBD is effective against the otherwise treatment-resistant cancer stem cells and joins a growing list of compounds effective against cancer stem cells. The effects and mechanisms of CBD in cancer stem cells should be further explored to find their Achilles heel.

scholarly journals Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aaron C. Raymond ◽  
Boning Gao ◽  
Luc Girard ◽  
John D. Minna ◽  
D. Gomika Udugamasooriya
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Preclinical Model ◽  
Small Subset ◽  
Structural Protein ◽  
Tumor Initiating Cells ◽  
Potential Biomarker ◽  
Lung Cancer Stem Cells

Abstract Tumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an “unbiased” peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells (defined by Aldefluor positivity), but not the remaining aldefluor negative cancer cells from the same preclinical model. One of the ‘hit’ peptoids bound to plectin, a structural protein, predominantly expressed intracellularly, but whose localization on the cell surface is linked to tumor invasion and metastasis. Our studies show both genotypic and phenotypic correlations between plectin and lung CSCs, as well as association of high plectin mRNA expression with poor patient survival in lung adenocarcinoma, potentially identifying plectin as a biomarker for lung CSCs.

Structural engineering to control density, conformation, and bioactivity of the poly(ethylene glycol)-grafted poly(urethane urea) scaffolds

2018 ◽  
Vol 34 (2) ◽  
pp. 209-223
Author(s):  
Shideh Shaneh ◽  
Fatemeh Shokrolahi ◽  
Parvin Shokrollahi ◽  
Hamid Yeganeh ◽  
Hossein Omidian
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ethylene Glycol ◽  
Structural Engineering ◽  
Cell Attachment ◽  
Poly Ethylene Glycol ◽  
Salt Leaching ◽  
The Matrix ◽  
Diphenyl Tetrazolium Bromide ◽  
Poly Ethylene

Poly(urethane urea) scaffolds were fabricated through combined salt leaching and solvent casting methods. The scaffolds were then functionalized via aminolysis with poly(ethylene glycol) (PEG- g-PUU). To compare its bioactivity, gelatin was also grafted onto the aminolyzed poly(urethane urea) surface (Gel- g-PUU). Chemical changes at the surface were then monitored using quantitative/qualitative methods. Grafting with both gelatin and poly(ethylene glycol) remarkably enhanced the wettability of poly(urethane urea). Proliferation of human adipose–derived mesenchymal stem cells on poly(urethane urea) and the modified poly(urethane urea)s was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. The cell experiment results showed that both the modified poly(urethane urea)s enhanced the attachment and proliferation of human adipose–derived mesenchymal stem cells compared to pure poly(urethane urea). Based on previous reports, while a supportive role is observed at adequate poly(ethylene glycol) graft densities, cell adhesion and proliferation are inhibited at very high grafting densities. To correlate the cell data to poly(ethylene glycol) conformations, the surface tension was measured. Data on human adipose–derived mesenchymal stem cells’ attachment/proliferation and contact angle/surface free energy together showed that the grafting density of poly(ethylene glycol) was regulated by optimizing aminolysis conditions, careful selection of poly(ethylene glycol)’s molecular weight, and bulk properties of the matrix poly(urethane urea). As a result, surface overcrowding and brush conformation of the poly(ethylene glycol) chains were avoided, and human adipose–derived mesenchymal stem cell attachment and proliferation occurred on the PEG- g-PUU scaffold at a comparable level to the Gel- g-PUU.

scholarly journals Targeting multiple genes containing long mononucleotide A-T repeats in lung cancer stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Narumol Bhummaphan ◽  
Piyapat Pin-on ◽  
Preeyaporn Plaimee Phiboonchaiyanan ◽  
Jirattha Siriluksana ◽  
Chatchawit Aporntewan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cell ◽  
Transcriptional Control ◽  
Single Gene ◽  
Repeat Sequence ◽  
Control Activity ◽  
Multiple Genes ◽  
Lung Cancer Stem Cells

Abstract Background Intratumour heterogeneous gene expression among cancer and cancer stem cells (CSCs) can cause failure of current targeted therapies because each drug aims to target the function of a single gene. Long mononucleotide A-T repeats are cis-regulatory transcriptional elements that control many genes, increasing the expression of numerous genes in various cancers, including lung cancer. Therefore, targeting A-T repeats may dysregulate many genes driving cancer development. Here, we tested a peptide nucleic acid (PNA) oligo containing a long A-repeat sequence [A(15)] to disrupt the transcriptional control of the A-T repeat in lung cancer and CSCs. Methods First, we separated CSCs from parental lung cancer cell lines. Then, we evaluated the role of A-T repeat gene regulation by counting the number of repeats in differentially regulated genes between CSCs and the parental cells of the CSCs. After testing the dosage and effect of PNA-A15 on normal and cancer cell toxicity and CSC phenotypes, we analysed genome-wide expression to identify dysregulated genes in CSCs. Results The number of A-T repeats in genes differentially regulated between CSCs and parental cells differed. PNA-A15 was toxic to lung cancer cells and CSCs but not to noncancer cells. Finally, PNA-A15 dysregulated a number of genes in lung CSCs. Conclusion PNA-A15 is a promising novel targeted therapy agent that targets the transcriptional control activity of multiple genes in lung CSCs.

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