Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line

Jakubowicz-Gil, Joanna; Langner, Ewa; Wertel, Iwona; Piersiak, Tomasz; Rzeski, Wojciech

doi:10.1016/j.cbi.2010.07.015

Cited by 66 publications

(60 citation statements)

References 44 publications

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“…Recent reports have shown that temozolomide killed brain tumor cells with greater efficiency when used in combination with epigallocatechin gallate (EGCG), a component of green tea or quercetin [12,40]. However, in our studies, rosehip extracts consistently demonstrated a greater capacity to reduce cell prolifera-tion than temozolomide (Figure 10).…”

Section: Discussionmentioning

confidence: 47%

“…Quercetin, a flavonoid, has been reported as one of the active ingredients that can be elucidated from rosehip extracts [12,13,38]. Purified quercetin has been tested against U-87MG, U-251 MG and A-172 cells [38].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have investigated the anti-oncogenic properties of natural products and several of these studies have shown that natural product extracts exhibit anti-oncogenic properties against various types of cancer [3][4][5][6][7]. Specifically, there has been a renewed effort to examine the anti-oncogenic properties of natural products for the treatment of GBM cells [8][9][10][11][12][13]. However, the anti-oncogenic properties of rosehip extracts on GBM cells have not been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Cagle¹,

Idassi²,

Carpenter³

et al. 2012

JCT

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Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL -25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 µM) or AKT (LY294002, 20 µM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL -25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 µM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Cagle¹,

Idassi²,

Carpenter³

et al. 2012

JCT

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“…The combination of quercetin and TMZ has been reported to treat the human astrocytoma cell line MOGGCCM (WHO grade III). The results indicate that quercetin acts in synergy with TMZ and that when both drugs are used in combination, rather than in separate pharmacological application, they more effectively induce programmed cell death [24] . However, glioblastoma cells (WHO grade IV) are usually TMZ-insensitive and multidrug resistant; thus, investigating the effects of quercetin and TMZ on glioblastoma cell lines is more meaningful.…”

Section: Discussionmentioning

confidence: 79%

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27

Sang

Lan

2014

Acta Pharmacol Sin

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Aim: Quercetin is an effective Hsp27 inhibitor and has been reported to facilitate tumor cell apoptosis. The aim of this study was to investigate whether quercetin could sensitize human glioblastoma cells to temozolomide (TMZ) in vitro. Methods: Both U251 and U87 human glioblastoma cells were treated with quercetin and/or TMZ for 48 h. Cell viability was detected using the MTT assay. Cell apoptosis was analyzed with caspase-3 activity kits and flow cytometry. Hsp27 expression and phosphorylation were examined using Western blot analysis. RNA interference using Hsp27 siRNA oligos was performed to knock down the gene expression of Hsp27. Results: TMZ (200 or 400 μmol/L) alone effectively inhibited the viability of U251 and U87 cells. When combined with quercetin (30 μmol/L), TMZ (100 μmol/L) significantly inhibited the cell viability, and the inhibition of TMZ (200 and 400 μmol/L) was enhanced. TMZ or quercetin anole did not affect caspase-3 activity and cell apoptosis, while TMZ combined with quercetin significantly increased caspase-3 activity and induced cell apoptosis. TMZ anole significantly increased Hsp27 phosphorylation in U251 and U87 cells, while quercetin or Hsp27 siRNA oligos combined with TMZ attenuated TMZ-induced Hsp27 phosphorylation and significantly inhibited Hsp27 expression. Conclusion: Combined treatment with TMZ and quercetin efficiently suppressed human glioblastoma cell survival in vitro.

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“…Data show means±standard errors calculated from three independent experiments. Asterisk (*) indicates significant change of protein expression using one-way ANOVA and Dunnett's posttest glioma cell line (MOGGCCM, astrocytoma GIII), a previous study showed an inhibition of HSPB1 and HSPA1A expression after treatment with TMZ, alone or in combination with quercetine (Jakubowicz-Gil et al 2010). This is indicating that TMZ is inducing different responses in different glioma cells, and the molecular heterogeneity may be important in understanding how current therapeutic treatments fail to target cells in the GBM tumor mass thereby selecting for resistant cells that can result in disease recurrence and poor survival (Chorny et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Effects of temozolomide (TMZ) on the expression and interaction of heat shock proteins (HSPs) and DNA repair proteins in human malignant glioma cells

Castro

Cayado-Gutiérrez

Zoppino

et al. 2015

Cell Stress and Chaperones

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We previously reported the association of HSPA1A and HSPB1 with high-grade astrocytomas, suggesting that these proteins might be involved in disease outcome and response to treatment. With the aim to better understand the resistance/susceptibility processes associated to temozolomide (TMZ) treatment, the current study was performed in three human malignant glioma cell lines by focusing on several levels: (a) apoptotic index and senescence, (b) DNA damage, and (c) interaction of HSPB1 with players of the DNA damage response. Three human glioma cell lines, Gli36, U87, and DBTRG, were treated with TMZ evaluating cell viability and survival, apoptosis, senescence, and comets (comet assay). The expression of HSPA (HSPA1A and HSPA8), HSPB1, O 6 -methylguanine-DNA methyltransferase (MGMT), MLH1, and MSH2 was determined by immunocytochemistry, immunofluorescence, and Western blot. Immunoprecipitation was used to analyze protein interaction. The cell lines exhibited differences in viability, apoptosis, and senescence after TMZ administration. We then focused on Gli36 cells (relatively unstudied) which showed very low recovery capacity following TMZ treatment, and this was related to high DNA damage levels; however, the cells maintained their viability. In these cells, MGMT, MSH2, HSPA, and HSPB1 levels increased significantly after TMZ administration. In addition, MSH2 and HSPB1 proteins appeared co-localized by confocal microscopy. This colocalization increased after TMZ treatment, and in immunoprecipitation analysis, MSH2 and HSPB1 appeared interacting. In contrast, HSPB1 did not interact with MGMT. We show in glioma cells the biological effects of TMZ and how this drug affects the expression levels of heat shock proteins (HSPs), MGMT, MSH2, and MLH1. In Gli36 cells, the results suggest that interactions between HSPB1 and MSH2, including co-nuclear localization, may be important in determining cell sensitivity to TMZ.

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Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line

Cited by 66 publications

References 44 publications

Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27

Effects of temozolomide (TMZ) on the expression and interaction of heat shock proteins (HSPs) and DNA repair proteins in human malignant glioma cells

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Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line

Cited by 66 publications

References 44 publications

Effect of Rosehip (&lt;i&gt;Rosa Canina&lt;/i&gt;) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Effect of Rosehip (&lt;i&gt;Rosa Canina&lt;/i&gt;) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27

Effects of temozolomide (TMZ) on the expression and interaction of heat shock proteins (HSPs) and DNA repair proteins in human malignant glioma cells

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Product

Resources

About

Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Effect of Rosehip (<i>Rosa Canina</i>) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis