Temozolomide and sorafenib as programmed cell death inducers of human glioma cells

Jakubowicz-Gil, Joanna; Bądziul, Dorota; Langner, Ewa; Wertel, Iwona; Zając, Adrian; Rzeski, Wojciech

doi:10.1016/j.pharep.2017.03.008

Cited by 32 publications

(38 citation statements)

References 18 publications

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“…Glioma is an aggressive brain tumor that exhibits high resistance to chemotherapy [20]. The functional effects of lncRNAs have been verified, including their role as key regulators of translational and transcriptional products that influence cellular functions [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway

Han

Wen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Spinal cord glioma is a highly aggressive malignancy that commonly results in high mortality due to metastasis, high recurrence and limited treatment regimens. This study aims to elucidate the effects of long non-coding RNA LINC01260 (LINC01260) on the proliferation, migration and invasion of spinal cord glioma cells by targeting Caspase recruitment domain family, member 11 (CARD11) via nuclear factor kappa B (NF-κB) signaling. Methods: The Multi Experiment Matrix (MEM) website was used for target gene prediction, and the DAVID database was used for analysis of the relationship between CARD11 and the NF-κB pathway. In total, 60 cases of glioma tissues and adjacent normal tissues were collected. Human U251 glioma cells were grouped into blank, negative control (NC), LINC01260 vector, CARD11 vector, siRNA-LINC01260, siRNA-CARD11, LINC01260 vector + CARD11 vector and LINC01260 + siRNA-CARD11 groups. A dual-luciferase reporter assay was conducted to verify the target relationship between LINC01260 and CARD11. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess expression of LINC01260, E-cadherin, p53, CARD11, Ki67, N-cadherin, matrix metalloproteinase (MMP)-9, NF-κBp65 and NF-κBp50. MTT, flow cytometry, wound-healing and Transwell assays were performed to examine cell viability, the cell cycle, apoptosis, invasion and migration. Tumor growth was assessed through xenografts in nude mice. Results: CARD11 was confirmed to be a target gene of LINC01260 and was found to be involved in regulating the NF-κB pathway. Compared with adjacent normal tissues, glioma tissues showed reduced expression of LINC01260 and elevated expression of CARD11 and genes related to apoptosis, invasion and migration; activation of NF-κB signaling was also observed. In contrast to the blank and NC groups, an elevated number of cells arrested in G1 phase, increased apoptosis and reduced cell proliferation, invasion and number of cells arrested in S and G2 phases, as well as tumor growth were found for the LINC01260 vector and siRNA-CARD11 groups. Conclusions: Our findings demonstrate that overexpression of LINC01260 inhibits spinal cord glioma cell proliferation, migration and invasion by targeting CARD11 via NF-κB signaling suppression.

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Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway

Han

Wen

et al. 2018

Cell Physiol Biochem

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“…However, phase I, II and III clinical trials have demonstrated a modest efficacy with this antiangiogenic drug, alone or in combination (Gerstner et al, ; Nabors et al, ). Instead, sorafenib has been used in combination with temozolomide as programmed cell‐death inducers of human glioma cells (Jakubowicz‐Gil et al, ). Sorafenib (Sb) is a multiple kinase inhibitor (from BRAF, VEGFR, PDGFR pathways) that targets both tumor‐cell proliferation and angiogenesis.…”

Section: Therapeutic Approaches Focused On Ecm and Invasionmentioning

confidence: 99%

“…However, phase I, II and III clinical trials have demonstrated a modest efficacy with this antiangiogenic drug, alone or in combination (Gerstner et al, 2015;Nabors et al, 2015). Instead, sorafenib has been used in combination with temozolomide as programmed cell-death inducers of human glioma cells (Jakubowicz-Gil et al, 2017).…”

Section: Th Er a P Eu Ti C A Pp R Oa Ch Es F Ocu S E D On Ec M An Dmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

166

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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“…Thus, prolonged 17 TMZ treatment is a relevant option either as up-front or as adjuvant treatment. 18 Clinical trials have shown a similar efficacy of TMZ vs RT for 1p/19q-codeleted 19 tumors [11,12]. Also, RT is associated with late neurocognitive toxicity.…”

Section: Introductionmentioning

confidence: 98%

“…The second one was lethally damaged tumor cells because of the action of 58 the therapy D(t). Temozolomide effect on proliferative cells is a complex one, leading 59 to death through different 'programmes' [18][19][20]. We put together the different 60 processes into two groups, each described by a term in our equations.…”

mentioning

confidence: 99%

Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas

Pérez-Garcı́a

Ayala-Hernández

Belmonte-Beitia

et al. 2019

Preprint

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The use of mathematical models for personalization of cancer therapies and raising hypothesis of potential clinical impact is an emerging topic in the interface between mathematics and oncology. Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model described the longitudinal volumetric dynamics of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutical strategies were tried computationally on the 'in-silico twins' of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive cycles had either the same or better long-term efficacy than the standard 28-day cycles. The results were confirmed in a large virtual clinical trial including 2000 patients. These long-cycle schemes would also have reduced toxicity and defer the appearance of resistances.On the basis of those results, a combination scheme consisting of five induction TMZ cycles given monthly plus 12 maintenance cycles given every three months was found to provide substantial survival benefits for the in-silico twins of the 11 LGO patients (median 5.69 years, range: 0.67 to 68.45 years) and in a large virtual trial including 2000 patients. This scheme could be useful for defining a standardized TMZ treatment for LGO patients with survival benefits.

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Temozolomide and sorafenib as programmed cell death inducers of human glioma cells

Abstract: Sorafenib and Temozolomide applied in combination are potent apoptosis inducers in T98G and MOGGCCM cells. ER stress precedes the elimination. Blocking of Hsp expression has a greater impact on ER stress rather than apoptosis induction.

Cited by 32 publications

References 18 publications

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway

Glioma infiltration and extracellular matrix: key players and modulators

Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas

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