Therapeutic approach of Cancer stem cells (CSCs) in gastric adenocarcinoma; DNA methyltransferases enzymes in cancer targeted therapy

Norollahi, Syedeh Elham; Mansour-Ghanaei, Fariborz; Joukar, Farahnaz; Ghadarjani, Shervin; Mojtahedi, Kourosh; Nejad, Kaveh Gharaei; Hemmati, Hossein; Gharibpoor, Faeze; Khaksar, Roya; Samadani, Ali Akbar

doi:10.1016/j.biopha.2019.108958

Cited by 24 publications

(15 citation statements)

References 98 publications

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“…However, when the damage exceeds capacity of DNA repair, apoptosis will be triggered, further leading to tumor cell death. Generally, the activation of DDR is implicated in radio-resistance of the GSCs and it involved a range of DNA damages related proteins such as ataxia telangiectasia Rad3-related (ATR), which initiates a transduction cascade activating downstream effectors, including H2AX histone, 53 binding protein 1 (53BP1), and the checkpoint kinases Checkpoint 1 (CHK1) and Checkpoint 2 (CHK2) (Kastan and Bartek, 2004;Norollahi et al, 2019). It has been reported that there was an aberrant constitutive activation of DDR by upregulation of related proteins under DNA replication stress produced by oncogenes in GBM (Bartkova et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…However, GBM is well documented for its rapid recurrence following radiotherapy, due to inadequate killing of cancer stem cells, which is known as tumor-initiating cells or tumor-propagating cells. CD133 is a pentaspan transmembrane protein and was commonly used as a glioblastoma stem cells (GSCs) biomarker, it has been showed that CD133 positive (CD133+) glioblastoma cells contributes to glioma radioresistance and tumor progress through preferential checkpoint response and DNA repair (Beier et al, 2007;Norollahi et al, 2019). In vivo and in vitro studies have also verified the fraction of CD133+ glioma cells were significantly increased after radiation treatment (Ahmed et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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A Brain-Penetrating Hsp90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

Chen

Gong

et al. 2020

Front. Pharmacol.

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Glioblastoma multiforme (GBM) is a highly heterogeneous disease, which is initiated and sustained by various molecular alterations in an array of signal transduction pathways. Heat-shock protein 90 (Hsp90) is a molecular chaperone and is critically implicated in folding and activation of a diverse group of client proteins, many of which are key regulators for glioblastoma biology. We here assessed the anti-neoplastic efficacy of a novel brain-penetrating Hsp90 inhibitor NXD30001 as a monotherapy and combined with radiation in vitro and in vivo. Our results demonstrated that NXD30001 potently inhibited neurosphere formation, growth, and survival of CD133+ GBM cells with the half maximal inhibitory concentration at low nanomolar range, but CD133− GBM cells were less sensitive to NXD30001. NXD30001 also increased radio-sensitivity in glioblastoma stem cells (GSCs) at suboptimal concentrations. Moreover, NXD30001 dose-dependently decreased phosphorylation levels of multiple Hsp90 client proteins which play key roles in GBM, such as EGFR, Akt, c-Myc, and Notch1. In addition, NXD30001 could impair DNA damage response and endoplasmic reticulum stress response after radiotherapy by alteration of the related proteins expression. In a murine orthotopic model of human glioblastoma, NXD30001 marvelously induced tumor regression and extended median survival of tumor-bearing mice by approximately 20% when compared with the vehicle group (37 d vs 31 d, P<0.05). Radiotherapy solely increased median survival of tumorbearing mice from 31 d to 38 d (P<0.05), while NXD30001 combined with radiation further extended survival to 43 d (P<0.05). We concluded that GSCs are more sensitive to NXD30001 than non-stem GBM cells, and NXD30001 in combination with radiation exerts better inhibitive effect in GBM progression than monotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Brain-Penetrating Hsp90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

Chen

Gong

et al. 2020

Front. Pharmacol.

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“…Epigenetics consist of DNA methylation, histone modification, histone acetylation, histone phosphorylation and also RNA remodeling which DNA methylation is the most important element [6][7][8][9][10][11][12]. Meanwhile, alongside with the investigation of epigenetics fluctuation in GI cancers, gene expression study must be added in order to have a better comparison and result [13][14][15][16][17][18][19][20].…”

Section: Epigenetic and Cancermentioning

confidence: 99%

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer

Babaei¹,

Khaksar²,

Zeinali³

et al. 2019

BioMedicine

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Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Meaningly, DNA methylation is identified as one of most important epigenetic regulators in gene expression and is considered as a notable potential driver in tumorigenesis and carcinogenesis through gene-silencing of tumor suppressors genes. Abnormal methylation situation, even in the level of promoter regions, does not essentially change the gene expression levels, particularly if the gene was become silenced, leaving the mechanisms of methylation without any response. According to the methylation situation which has a strong eagerness to be highly altered on CpG islands in carcinogenesis and tumorigenesis, considering its epigenetic fluctuations in finding new biomarkers is of great importance. Modifications in DNA methylation pattern and also enrichment of methylated histone signs in the promoter regions of some certain genes like MUTYH, KLF4/6 and WNT1 in different signaling pathways could be a notable key contributors to the upregulation of tumor initiation in CRC. These epigenetic alterations could be employed as a practical diagnostic biomarkers for colorectal cancer. In this review, we will be discuss these fluctuations of MUTYH, KLF4/6 and WNT1 genes in CRC.

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“…Hypermethylation of tumor suppressor genes plays a determinative role in carcinogenesis; thus, inhibitors of DNA methylation are taken seriously in molecular therapy [73]. Moreover, the inhibition of DNA methyltransferase (DNMT) can reduce the tumorigenicity of GCSCs [74]. Some potential CSC-related factors are known.…”

Section: Current Target and Future Direction Of Gcsc Treatmentmentioning

confidence: 99%

Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets

Yasuda

et al. 2020

Biomedicines

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Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) are known to be involved in chemotherapy resistance and the development of metastases. Although CSCs harbor self-renewal and tumorigenic abilities, the immune microenvironment surrounding CSCs provides various factors and supports the maintenance of CSC properties. The current review summarizes the accumulating findings regarding the relationship between the immune microenvironment and gastric CSCs (GCSCs), which will support the possibility of developing novel therapeutic strategies for targeting GCSCs.

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Therapeutic approach of Cancer stem cells (CSCs) in gastric adenocarcinoma; DNA methyltransferases enzymes in cancer targeted therapy

Cited by 24 publications

References 98 publications

A Brain-Penetrating Hsp90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

A Brain-Penetrating Hsp90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer

Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets

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