Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

Santangelo, Rosa; Rizzarelli, Enrico; Copani, Agata

doi:10.1021/acsomega.9b04483

Cited by 8 publications

(8 citation statements)

References 57 publications

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“…Glioblastoma cells were treated with the highest DOX concentration—15 µM ( Figure 4 ). The resistance of U87 cells considered as sensitive in our model is probably due to the deregulation of the cell cycle and the absence of apoptosis [ 24 ]. The death of tested sensitive cells (NCI-H460, DLD1 and U87) occurred after 80, 85 and 15 min (respectively) of drug injection ( Figure 2 , Figure 3 and Figure 4 ), and the corresponding drops in variance were statistically significant ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

et al. 2021

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Background and Objectives: Optimization of chemotherapy is crucial for cancer patients. Timely and costly efficient treatments are emerging due to the increasing incidence of cancer worldwide. Here, we present a methodology of nano-motion analysis that could be developed to serve as a screening tool able to determine the best chemotherapy option for a particular patient within hours. Materials and Methods: Three different human cancer cell lines and their multidrug resistant (MDR) counterparts were analyzed with an atomic force microscope (AFM) using tipless cantilevers to adhere the cells and monitor their nano-motions. Results: The cells exposed to doxorubicin (DOX) differentially responded due to their sensitivity to this chemotherapeutic. The death of sensitive cells corresponding to the drop in signal variance occurred in less than 2 h after DOX application, while MDR cells continued to move, even showing an increase in signal variance. Conclusions: Nano-motion sensing can be developed as a screening tool that will allow simple, inexpensive and quick testing of different chemotherapeutics for each cancer patient. Further investigations on patient-derived tumor cells should confirm the method’s applicability.

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Section: Resultsmentioning

confidence: 99%

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

et al. 2021

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“…Lonafarnib (LNF; Sigma Aldrich) and Temozolomide (TMZ; Sigma Aldrich) were reconstituted in DMSO according to the manufacturer's protocol and were diluted in culture media for treatment. At Day 7, GBM:astrocytes, GBM:EC, and triculture MCTS were treated with 5 μM LNF, 100 μM TMZ or their combination (5 μM LNF + 100 μM TMZ) for 48 h. These concentrations were chosen based on previous studies that have demonstrated that TMZ (100 μM) targeted MGMT and telomerase activity, and LNF (5 μM) inhibited the neurosphere formation in GBM cells 25,27–34 …”

Section: Methodsmentioning

confidence: 99%

“…At Day 7, GBM:astrocytes, GBM:EC, and triculture MCTS were treated with 5 μM LNF, 100 μM TMZ or their combination (5 μM LNF + 100 μM TMZ) for 48 h. These concentrations were chosen based on previous studies that have demonstrated that TMZ (100 μM) targeted MGMT and telomerase activity, and LNF (5 μM) inhibited the neurosphere formation in GBM cells. 25,[27][28][29][30][31][32][33][34] 2.4 | Optical microscopy and image analysis 3D MCTS were monitored using an Olympus IX83 microscope with a spinning disc confocal attachment. The size and the cross-sectional area of the spheroids were analyzed using ImageJ software (NIH) as described previously.…”

Section: Drug Treatmentmentioning

confidence: 99%

The impact of temozolomide and lonafarnib on the stemness marker expression of glioblastoma cells in multicellular spheroids

Nakod

Kondapaneni

Edney

et al. 2022

Biotechnology Progress

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Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis. The GBM microenvironment is highly heterogeneous and is composed of many cell types including astrocytes and endothelial cells (ECs) along with tumor cells, which are responsible for heightened resistance to standard chemotherapeutic drugs such as Temozolomide (TMZ). Here, we investigated how drug treatments impact stemness marker expression of GBM cells in multicellular tumor spheroid (MCTS) models. Co‐ and tri‐culture MCTS constructed using U87‐MG GBM cells, astrocytes, and/or ECs were cultured for 7 days. At Day 7, 5 μM lonafarnib (LNF), 100 μM TMZ, or combination of 5 μM LNF + 100 μM TMZ was added and the MCTS were cultured for an additional 48 h. We assessed the spheroid sizes and expression of stemness markers‐ NESTIN, SOX2, CD133, NANOG, and OCT4‐ through qRT‐PCR and immunostaining. Following 48 h treatment with LNF, TMZ or their combination (LNF + TMZ), the spheroid sizes decreased compared to the untreated control. We also observed that the expression of most of the stemness markers significantly increased in the LNF + TMZ treated condition as compared to the untreated condition. These results indicate that drug treatment can influence the stemness marker expression of GBM cells in MCTS models and these aspects must be considered while evaluating therapies. In future, by incorporating other relevant cell types, we can further our understanding of their crosstalk, eventually leading to the development of new therapeutic strategies.

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“…To obtain TMZ (Sigma, 76899, USA) resistant cell lines, we gradually increased the exposure of U87 cells from 5 to 100 μmol/l of TMZ. The TMZ-resistant U87 cells were named U87/R cells 29 .…”

Section: Methodsmentioning

confidence: 99%

Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p

Liu

Chen

et al. 2021

Cell Death Dis

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Temozolomide (TMZ) is the internationally recognized and preferred drug for glioma chemotherapy treatment. However, TMZ resistance in glioma appears after long-term use and is an urgent problem that needs to be solved. Circular RNAs (circRNAs) are noncoding RNAs and play an important role in the pathogenesis and progression of tumors. Hsa_circ_0110757 was identified in TMZ-resistant glioma cells by high-throughput sequencing analysis and was derived from reverse splicing of myeloid cell leukemia-1 (Mcl-1) exons. The role of hsa_circ_0110757 in TMZ-resistant glioma was evaluated both in vitro and in vivo. It was found that hsa_circ_0110757 and ITGA1 are more highly expressed in TMZ-resistant glioma than in TMZ-sensitive glioma. The overexpression of hsa_circ_0110757 in glioma patients treated with TMZ was obviously associated with tumor invasion. This study indicates that hsa_circ_0110757 inhibits glioma cell apoptosis by sponging hsa-miR-1298-5p to promote ITGA1 expression. Thus, hsa_circ_0110757/hsa-miR-1298-5p/ITGA could be a potential therapeutic target for reversing the resistance of glioma to TMZ.

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Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

Cited by 8 publications

References 57 publications

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

The impact of temozolomide and lonafarnib on the stemness marker expression of glioblastoma cells in multicellular spheroids

Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p

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