scholarly journals Curcumin suppresses LGR5(+) colorectal cancer stem cells by inducing autophagy and via repressing TFAP2A-mediated ECM pathway

2021 ◽  
Author(s):  
Xiaohong Mao ◽  
Xin Zhang ◽  
Xiaowei Zheng ◽  
Yongwu Chen ◽  
Zixue Xuan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Marker Gene ◽  
Stem Cell Marker ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Cell Proliferation Inhibition ◽  
Colorectal Cancer Stem Cells

Abstract Colorectal cancer stem cells (CSCs) have the potential for self-renewal, proliferation, and differentiation. And LGR5 is a stem cell marker gene of colorectal cancer. Curcumin can suppress oncogenicity of many cancer cells, yet the effect and mechanism of curcumin in LGR5(+) colorectal cancer stem cells (CSCs) have not been studied. In this study, we studied the effect of curcumin on LGR5(+) colorectal CSCs using the experiments of tumorsphere formation, cell viability and cell apoptosis. Then autophagy analysis, RNA-Seq, and real-time PCR were used to identify the mechanism responsible for the inhibition of LGR5(+) colorectal CSCs. Our results showed that curcumin inhibited tumorsphere formation, decreased cell viability in a dose-dependent manner, and also promoted apoptosis of LGR5(+) colorectal CSCs. Next, we found curcumin induced autophagy of LGR5(+) colorectal CSCs. When LGR5(+) colorectal CSCs were co-treated with curcumin and the autophagy inhibitor (hydroxychloroquine), curcumin-induced cell proliferation inhibition decreased. In addition, we also found that curcumin inhibited the extracellular matrix (ECM)-receptor interaction pathway via the downregulation of the following genes: GP1BB, COL9A3, COMP, AGRN, ITGB4, LAMA5, COL2A1, ITGB6, ITGA1, and TNC. Further, these genes were transcriptionally regulated by TFAP2A, and the high expression of TFAP2A was associated with poor prognosis in colorectal cancer. In conclusion, curcumin suppressed LGR5(+) colorectal CSCs, potentially by inducing autophagy and repressing the oncogenic TFAP2A-mediated ECM pathway. Graphic abstract

scholarly journals Suppressive Effect of α-mangostin for Cancer Stem Cells in Colorectal Cancer via the Notch Pathway

2021 ◽  
Author(s):  
Min Kyoung Jo ◽  
Chang Mo Moon ◽  
Eun Ju Kim ◽  
Jee Hee Kwan ◽  
Xiang Fei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Suppressive Effect ◽  
Notch Signaling Pathway ◽  
Dependent Manner

Abstract Background: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. Methods: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. Results: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. Conclusion: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU–induced augmentation of CSCs via the Notch signaling pathway.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer

2021 ◽  
Author(s):  
Yingru Zhang ◽  
Chunpu Li ◽  
Ru Jia ◽  
Ruixuan Gao ◽  
Yiyang Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Amino Acid ◽  
Cancer Stem Cells ◽  
Drug Release ◽  
Signaling Pathway ◽  
Water Solubility ◽  
Sustained Drug Release ◽  
Colorectal Cancer Stem Cells ◽  
Micelle System

A new nano-micelle system with better water solubility and sustained drug release effect, targeting colorectal cancer stem cells, effectively inhibits the growth and metastasis of colorectal cancer via the Wnt/β-catenin signaling pathway.

Brg1 is required to maintain colorectal cancer stem cells

2021 ◽  
Author(s):  
Takaaki Yoshikawa ◽  
Akihisa Fukuda ◽  
Mayuki Omatsu ◽  
Mio Namikawa ◽  
Makoto Sono ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Colorectal Cancer Stem Cells

Abstract 1083: A novel role of SRC in mediating bypass resistance to MEK inhibition in colorectal cancer stem cells

2021 ◽  
Author(s):  
Mingli Yang ◽  
Thomas B. Davis B. Davis ◽  
Michael V. Nebozhyn ◽  
Andrey Loboda ◽  
Heiman Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Mek Inhibition ◽  
Colorectal Cancer Stem Cells

CDC25A is Strongly Associated with Colorectal Cancer Stem Cells and Poor Clinical Outcome of Patients

Gene Reports ◽  
2021 ◽  
pp. 101415
Author(s):  
Hamed Manoochehri ◽  
Shafagh Asadi ◽  
Hamid Tanzadehpanah ◽  
Mohsen Sheykhhasan ◽  
Masoud Ghorbani
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Clinical Outcome ◽  
Poor Clinical Outcome ◽  
Colorectal Cancer Stem Cells
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