Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas

Zhen, Yunbo; Zhao, Shen; Li, Qiang; Li, Yang; Kawamoto, Keiji

doi:10.1016/j.canlet.2009.11.005

Cited by 67 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of note, silencing of Notch1 signaling reduced the self-renewal capacity, enhanced the sensitivity of SP cells to DNA-targeting chemotherapeutic drugs and the expression of stemness genes was also significantly downregulated. Consistent with these findings, previous studies on different cancer types demonstrated that Notch-depleted SP cells were more sensitive to chemotherapy and apoptosis, and that their self-renewal ability and high proliferation rate were also compromised (22)(23)(24)(25). All of these results suggested that Notch1 signaling has a crucial role in drug resistance and maintenance of self-renewal of SP cells.…”

Section: Discussionsupporting

confidence: 84%

Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

Jiang

Zhan

2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Upregulation of the Notch signaling pathway in cancer stem cells and side population (SP) cells has a major role in maintenance, self-renewal and chemoresistance. The present study isolated a cancer stem cell-like SP accounting for 4.1% of a glioblastoma cell population using a Hoechst 33342 dye exclusion assay. In this glioblastoma SP, the expression of of Notch1 signaling proteins Notch1 intracellular domain and Hes-1 was markedly upregulated. Furthermore, knockdown of Notch1 by RNA interference significantly diminished the neurosphere formation ability, self-renewal and chemoresistance of the SP cells. In addition, the expression of the stem-cell surface genes Oct-4, Sox2 and Nanog in SP cells was significantly reduced and the sensitivity to the SP cells to chemotherapeutics was enhanced following Notch1 knockdown. In conclusion, the results of the present study suggested that upregulation of Notch1 is involved in the chemotherapy resistance and tumor recurrence of glioblastoma. Hence, the development of novel anti-cancer drugs targeting the Notch1 signaling pathway may be a promising strategy for curing glioblastoma.

show abstract

Section: Discussionsupporting

confidence: 84%

Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

Jiang

Zhan

2016

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…In addition, the self-renewal and high proliferation rate was compromised in the Notch depleted cells. In consistence with the previous studies (Zhang et al, 2004;Fan et al, 2008;Sikandar et al, 2010;Zhen et al, 2010), we also demonstrated that sorted NPC SP cells possess elevated Notch1 pathways as the expression level of NCID, Notch1 and Hes-1 are up regulated in side population cells. Simultaneously, the activation of Notch1 pathways leads to the over expression of stem cell genes such as Oct-4, Sox2 and Nanong and thus essential for self-renewal property of SP cells.…”

Section: Discussionsupporting

confidence: 92%

Notch 1 signaling pathway is the potential target of novel anticancer drugs for the treatment of human nasopharyngeal cancer

Guan

Zhang

Ding

et al. 2014

Bangladesh J Pharmacol

View full text Add to dashboard Cite

IntroductionNasopharyngeal carcinoma is one of the most common cancers originate from the upper region of pharynx, occurs in both men and women among worldwide. Despite recent advances in treatment strategy, still patients are suffering from therapy failure, tumor recurrence and metastasis.According to the concept of cancer stem cell theory, tumors are heterogeneous and they contain small subpopulation of cells, which have indefinite life span, are termed as cancer stem cells. These cancer stem cells play a major role in tumorigenesis and also responsible for resistance to cancer therapies and tumor recurrence (Kawasaki et al., 2008). Several studies showed that cancer stem cells are highly self-renewal, possess differentiation potential, express stem cell surface proteins (e.g., CD24, CD44 and CD133), chemo-and apoptosis resistance. However, the molecular mechanism and signaling pathways behind the cancer stem cells mediated tumorigenesis is not clear. So far, studies in different cancers showed that Wnt/β-catenin and Notch signaling play a crucial role in self-renewal and maintenance of cancer stem cells. Notch signaling is highly activated in cancer stem cells and thus leads to the over expression of stem cell proteins which contributed to rapid propagation of cancer stem cells (Pannuti et al., 2010;Wang et al., 2005;Zhang et al., 2010;Teng et al., 2010;Bao et al., 2006). Studies also demonstrated in nasopharyngeal carcino-ma cell line that inactivation of Notch signaling leads to increased sensitivity of nasopharyngeal carcinoma side AbstractActivation of Notch signaling pathway in cancer stem cells plays a crucial role in the regulation of self-renewal and maintenance of side population cells. In the present study, we have identified cancer stem like 2.7% side population cells from nasopharyngeal carcinoma samples whose prevalence was significantly reduced to 0.3% upon verapamil treatment. The protein level of Notch1 and Hes-1 are highly up-regulated in fluorescence-activated cell sorting purified side population cells and thus leads to the elevated expression of stem cell surface proteins (Oct-4, Sox2 and Nanog), which are essential for side population cells self-renewal. In addition, these nasopharyngeal carcinoma side population cells are CD133 and CD44 positive and they possess enhanced cell proliferation rate, highly tumorgenic and invasive. Our findings suggest that Notch1 signaling is a potential target of novel anticancer drugs, which could efficiently target and eradicate the cancer stem cells. Article Info

show abstract

“…[55][56][57] If active Notch signaling in the same way plays a role in maintenance of the immature state of the bCSC population in the culture but is not essential for the growth of GBM neurosphere cells in vivo, one might speculate that Notch inhibition merely leads to differentiation of the bCSC cells as previously has been demonstrated, 16,17,58 rather than killing them as others have suggested. 18 In line with this, it has been demonstrated that some GSIs, including DAPT, are unable to kill bCSC.…”

Section: Discussionmentioning

confidence: 85%

Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature

Kristoffersen

Nedergaard

Villingshøj

et al. 2014

Cancer Biology & Therapy

View full text Add to dashboard Cite

Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas

Cited by 67 publications

References 33 publications

Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

Notch 1 signaling pathway is the potential target of novel anticancer drugs for the treatment of human nasopharyngeal cancer

Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature

Contact Info

Product

Resources

About