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 Cancer Stem Cells, Quo Vadis? The Notch Signaling Pathway in Tumor Initiation and Progression

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1879 ◽  
Author(s):  
Christian T. Meisel ◽  
Cristina Porcheri ◽  
Thimios A. Mitsiadis
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Adult Life ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Fine Tuning ◽  
Cell Fate Decisions

The Notch signaling pathway regulates cell proliferation, cytodifferentiation and cell fate decisions in both embryonic and adult life. Several aspects of stem cell maintenance are dependent from the functionality and fine tuning of the Notch pathway. In cancer, Notch is specifically involved in preserving self-renewal and amplification of cancer stem cells, supporting the formation, spread and recurrence of the tumor. As the function of Notch signaling is context dependent, we here provide an overview of its activity in a variety of tumors, focusing mostly on its role in the maintenance of the undifferentiated subset of cancer cells. Finally, we analyze the potential of molecules of the Notch pathway as diagnostic and therapeutic tools against the various cancers.

732 - Novel Marmelin Analog MRL16 Targets Notch Signaling Pathway in Colon Cancer Stem Cells

2018 ◽  
Vol 154 (6) ◽  
pp. S-151
Author(s):  
Dharmalingam Subramaniam ◽  
Sivapriya Ponnurangam ◽  
Prasad Dandawate ◽  
Ossama Tawfik ◽  
Roy A. Jensen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Colon Cancer Stem Cells

scholarly journals Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells

Oncotarget ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 3217-3232 ◽  
Author(s):  
Sivapriya Ponnurangam ◽  
Prasad R. Dandawate ◽  
Animesh Dhar ◽  
Ossama W. Tawfik ◽  
Rajashri R. Parab ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Pancreatic Cancer Stem Cells

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

Abstract 3227: Novel Marmelin analog DBQ targets Notch signaling pathway in colon cancer stem cells

2017 ◽  
Author(s):  
Dharmalingam Subramaniam ◽  
Sivapriya Ponnurangam ◽  
Prasad R. Dandawate ◽  
Gaurav Kaushik ◽  
Ossama W. Tawfik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Colon Cancer Stem Cells

scholarly journals All trans retinoic acid inhibits the gene expression of self-renewal and Notch signaling pathway in gastric cancer cells

2018 ◽  
Vol 34 (4) ◽  
Author(s):  
PHU HUNG NGUYEN ◽  
Thu Ha Ngo ◽  
Thi Binh Luu
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Retinoic Acid ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Self Renewal ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All trans retinoic acid (ATRA) plays an important role in many cellular processes and is a potent promising substance for cancer therapy. The self-renewal is a prominent feature of cancer stem cells that is tightly controlled by a number of specific genes, and is also mediated by the cell signaling pathways. The Notch signal pathway has been shown to be one of the few major molecular signaling pathways of cancer stem cells, which regulates self-renewal and survival of cancer stem cells. In this study, we showed that ATRA reduced the expression of important genes involved in self-renewal of cells including Sox2, KLF4, DMNT1 and MYC as well as TBGUT markers such as CD24, MUC1 and CD90. Furthermore, we indicate that the ATRA-induced expression of self-renewal genes and cancer stem cell markers of gastric cancer stem cells can be mediated by the regulation of the Notch signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document