Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme

Briceño, Eduardo; Carreño, Alejandra; Sotelo, Julio

doi:10.1016/j.surneu.2006.08.080

Cited by 108 publications

(88 citation statements)

References 16 publications

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“…Chloroquine has been used in several studies to suppress tumor growth, including in lung cancer cells (25). In GBM, the effects of chloroquine were promising and led to a significant extension of overall patient survival time (26).…”

Section: Discussionmentioning

confidence: 99%

Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner

et al. 2017

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Abstract. Despite major contributions to the current molecular understanding of autophagy, a recycling process for intracellular components to maintain homeostatic balance, relatively little is known about the interacting networks. To address this issue, the current study investigated the role of autophagy in primary and established glioblastoma multiforme (GBM) cells and its interplay with the epidermal growth factor receptor (EGFR) and the standard chemotherapeutic agent temozolomide (TMZ). TMZ treatment leads to an upregulation of autophagy, predominantly in primary GBM cells. The interaction between EGFR and Beclin-1, an important protein in initiating autophagy, was assessed using a cancer cell line transfected with EGFR vIII , and by stimulation with EGF. The results of the current study suggest that Beclin-1 and EGFR do not interact directly in either primary or established GBM cells. To enable the limited efficacy of patient treatment strategies of GBM to potentially be enhanced through the application of autophagy regulators, the multiple cellular interactions of autophagy require further elucidation.

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Section: Discussionmentioning

confidence: 99%

Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner

et al. 2017

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“…In a recent study, the quinolinebased antimalarial, CQ, in combination with conventional therapy significantly increased the mean survival probability of patients with GBM from 11.4 to 25 months. 4 The authors of that study attributed the antimutagenic properties of CQ to its ability to enhance TMZ. 5 They hypothesized that mutagenic chemotherapies, such as TMZ and carmustine, cause hypermutations in glioma cell clones that eventually lead to drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

Golden

Cho²,

Jahanian

et al. 2014

FOC

153

117

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Object In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen. Methods Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ. Results Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors. Conclusions Taken together, these results demonstrate that CQ blocks autophagy and triggers endoplasmic reticulum stress, thereby increasing the chemosensitivity of glioma cells to TMZ.

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“…This has attracted the use of autophagy inhibitors to enhance the efficacy of chemotherapy. Chloroquine, an autophagy inhibitor, has been reported to sensitise a variety of cancers to conventional chemotherapy in vitro and in vivo Solomon and Lee, 2009), and enhance survival of patients with glioblastoma multiforme when used as an adjuvant with conventional chemotherapy or radiotherapy (Briceno et al, 2007).…”

Section: Chloroquinementioning

confidence: 99%

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

2012

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Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme

Cited by 108 publications

References 16 publications

Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner

Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

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