Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

Liu, Junfeng; Gao, Qinglei; Xie, Tao; Liu, Yu; Luo, Longjun; Xu, Changwu; Shen, Lu; Wan, Feng; Lei, Ting; Ye, Fei

doi:10.1007/s10238-018-0504-7

Cited by 5 publications

(11 citation statements)

References 38 publications

(57 reference statements)

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“…However, several studies have suggested that most glioma cells display resistance to TRAIL-induced apoptosis (12,13), and to overcome this resistance is a critical issue. Among various investigations conducted, it has been reported that TRAIL-induced apoptosis can be enhanced by combination with other drugs or by irradiation (14–18,38). Combined treatment with TRAIL sensitizers is regarded as a promising strategy to overcome TRAIL resistance, and several attempts have been made to identify such TRAIL sensitizers (14–18).…”

Section: Discussionmentioning

confidence: 99%

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IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells

et al. 2019

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in cancer cells by binding to its receptors, death receptor 4 (DR4) and DR5, without affecting normal cells, and is therefore considered to be a promising antitumor agent for use in cancer treatment. However, several studies have indicated that most glioma cell lines display resistance to TRAIL-induced apoptosis. To overcome such resistance and to improve the efficacy of TRAIL-based therapies, identification of ideal agents for combinational treatment is important for achieving rational clinical treatment in glioblastoma patients. The main aim of this study was to investigate whether interferon-β (IFN-β) (with its pleiotropic antitumor activities) could sensitize malignant glioma cells to TRAIL-induced apoptosis using glioma cell lines. TRAIL exhibited a dose-dependent antitumor effect in all of the 7 types of malignant glioma cell lines, although the intensity of the effect varied among the cell lines. In addition, combined treatment with TRAIL (low clinical dose: 1 ng/ml) and IFN-β (clinically relevant concentration: 10 IU/ml) in A-172, AM-38, T98G, U-138MG and U-251MG demonstrated a more marked antitumor effect than TRAIL alone. Furthermore, the antitumor effect of the combined treatment with TRAIL and IFN-β may be enhanced via an extrinsic apoptotic system, and upregulation of DR5 was revealed to play an important role in this process in U-138MG cells. These findings provide an experimental basis to suggest that combined treatment with TRAIL and IFN-β may offer a new therapeutic strategy for malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

“…TRAIL induces apoptosis of cancer cells by binding to its receptors DR4 and DR5 (9). In malignant glioma cells, there have been indications that cisplatin and irradiation may upregulate the expression of DR5 (38,47). Conversely, in malignant glioma cells, IFN-β has been revealed to upregulate the expression of p53 (24).…”

Section: Discussionmentioning

confidence: 99%

IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells

et al. 2019

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“…CD133 is a cell marker commonly expressed in CSCs, such as in colorectal cancer (CRC) and glioma [ 13 ]. Other CSC markers include CD44, nestin, and sox-2, usually co-expressing with CD133 [ 9 , 23 ]. CD133-positive cells present high ATP-binding cassette transporter (ABCG5) expression related to chemoresistance [ 12 ].…”

Section: Trail Resistance Mechanismmentioning

confidence: 99%

“…Another TRAIL resistance mechanism associated with downregulation of the dead receptors DR4 and DR5 is overexpression of the decoy receptors DcR1 and DcR2 and overexpression of apoptosis inhibitors, such as cFLIP. It is suggested that activation of NF-kB could upregulate DR5 expression [ 9 ]. In turn, activation of the NF-kB pathway by TRAIL is associated with improvement of tumor growth, clonal expansion, and CSC signaling [ 6 ].…”

Section: Trail Resistance Mechanismmentioning

confidence: 99%

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Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL

Quiroz-Reyes,

Delgado-Gonzalez,

Islas

et al. 2021

Pharmaceutics

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. TRAIL has been widely studied as a novel strategy for tumor elimination, as cancer cells overexpress TRAIL death receptors, inducing apoptosis and inhibiting blood vessel formation. However, cancer stem cells (CSCs), which are the main culprits responsible for therapy resistance and cancer remission, can easily develop evasion mechanisms for TRAIL apoptosis. By further modifying their properties, they take advantage of this molecule to improve survival and angiogenesis. The molecular mechanisms that CSCs use for TRAIL resistance and angiogenesis development are not well elucidated. Recent research has shown that proteins and transcription factors from the cell cycle, survival, and invasion pathways are involved. This review summarizes the main mechanism of cell adaption by TRAIL to promote response angiogenic or pro-angiogenic intermediates that facilitate TRAIL resistance regulation and cancer progression by CSCs and novel strategies to induce apoptosis.

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Current approaches in enhancing TRAIL therapies in glioblastoma

Thang

Mellows

Mercer-Smith

et al. 2023

Neuro-Oncology Advances

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Glioblastoma (GBM) is the most prevalent, aggressive, primary brain cancer in adults and continues to pose major medical challenges due in part to its high rate of recurrence. Extensive research is underway to discover new therapies that target GBM cells and prevent the inevitable recurrence in patients. The pro-apoptotic protein tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has attracted attention as an ideal anti-cancer agent due to its ability to selectively kill cancer cells with minimal toxicity in normal cells. Although initial clinical evaluations of TRAIL therapies in several cancers were promising, later stages of clinical trial results indicated that TRAIL and TRAIL-based therapies failed to demonstrate robust efficacies due to poor pharmacokinetics, resulting in insufficient concentrations of TRAIL at the therapeutic site. However, recent studies have developed novel ways to prolong TRAIL bioavailability at the tumor site and efficiently deliver TRAIL and TRAIL-based therapies using cellular and nanoparticle vehicles as drug loading cargos. Additionally, novel techniques have been developed to address monotherapy resistance, including modulating biomarkers associated with TRAIL resistance in GBM cells. This review highlights the promising work to overcome the challenges of TRAIL-based therapies with the aim to facilitate improved TRAIL efficacy against GBM.

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Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

Cited by 5 publications

References 38 publications

IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells

IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells

Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL

Current approaches in enhancing TRAIL therapies in glioblastoma

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