Inhibition of the insulin-like growth factor 1 receptor by CHM-1 blocks proliferation of glioblastoma multiforme cells

Lin, Yingchao; Hou, Shin-Chen; Hung, Chao‐Ming; Lin, Jia-Ni; Chen, Wei-Chih; Ho, Chi‐Tang; Kuo, Sheng‐Chu; Way, Tzong‐Der

doi:10.1016/j.cbi.2015.01.016

Cited by 13 publications

(8 citation statements)

References 40 publications

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“…Overexpression of IGF-1R has also been associated with a higher tumor grade, inhibition of apoptosis, increased proliferation rate, and angiogenesis in patients with pancreatic ductal adenocarcinoma [6], and with a lower survival in patients with colorectal cancer [7]. Moreover, the IGF-1R signaling pathway is highly active in different types of human tumors, as is the case for metastatic melanoma [8], and is known to play a critical role in the transformation, growth and survival of glioblastoma multiforme (GBM) cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

Fuentes-Baile

Ventero

Encinar

et al. 2020

Cancers

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We have determined the effects of the IGF-1R tyrosine kinase inhibitors BMS-754807 (BMS) and OSI-906 (OSI) on cell proliferation and cell-cycle phase distribution in human colon, pancreatic carcinoma, and glioblastoma cell lines and primary cultures. IGF-1R signaling was blocked by BMS and OSI at equivalent doses, although both inhibitors exhibited differential antiproliferative effects. In all pancreatic carcinoma cell lines tested, BMS exerted a strong antiproliferative effect, whereas OSI had a minimal effect. Similar results were obtained on glioblastoma primary cultures, where HGUE-GB-15, -16 and -17 displayed resistance to OSI effects, whereas they were inhibited in their proliferation by BMS. Differential effects of BMS and OSI were also observed in colon carcinoma cell lines. Both inhibitors also showed different effects on cell cycle phase distribution, BMS induced G2/M arrest followed by cell death, while OSI induced G1 arrest with no cell death. Both inhibitors also showed different effects on other protein kinases activities. Taken together, our results are indicative that BMS mainly acts through off-target effects exerted on other protein kinases. Given that BMS exhibits a potent antiproliferative effect, we believe that this compound could be useful for the treatment of different types of tumors independently of their IGF-1R activation status.

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Section: Introductionmentioning

confidence: 99%

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

Fuentes-Baile

Ventero

Encinar

et al. 2020

Cancers

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“…Low protein intake is associated with a major decrease in levels of insulin-like growth factor-1 (IGF-1) [39], which we mimicked by serum restriction in the cell culture medium. Since the insulin-like growth factor receptor (IGF-1R) is overexpressed in different cancer cells [40,41,42] and the IGF-1-dependent pathway plays a major role in cancer cell proliferation, novel approaches aim to inhibit IGF-1R in cancer treatment [43]. Beyond that, OV replication has shown to rely on distinct pathways, e.g., poxvirus JX-594 replication was demonstrated to be limited in cells with activated EGFR/Ras signaling pathways [36,44].…”

Section: Discussionmentioning

confidence: 99%

Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus

Scheubeck

Berchtold

Smirnow

et al. 2019

Viruses

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Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.

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“…This genetic heterogeneity separates GBM subtypes and is defined by gene expression analysis. Novel therapeutic alternatives are now focused to increase the immune recognition and immune response ( 24 , 25 ), to block metabolism pathways ( 26 ), to knock genes ( 27 ), and to modulate cellular redox status ( 28 ).…”

Section: Gliomagenesismentioning

confidence: 99%

Role of Redox Status in Development of Glioblastoma

et al. 2016

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Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described.

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Inhibition of the insulin-like growth factor 1 receptor by CHM-1 blocks proliferation of glioblastoma multiforme cells

Cited by 13 publications

References 40 publications

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus

Role of Redox Status in Development of Glioblastoma

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