Preferential radiosensitization to glioblastoma cancer stem cell‑like cells by a Hsp90 inhibitor, N‑vinylpyrrolidone‑AUY922

Tani, Toshiaki; Tojo, Naomi; Ohnishi, Ken

doi:10.3892/ol.2022.13222

Cited by 4 publications

(4 citation statements)

References 31 publications

(30 reference statements)

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“…Despite the opposing findings on the effect of Hsp90 on the survival of patients, experimental studies show that inhibition of the Hsp90 ATPase domain with Shepherdin, a peptidomimetic antagonist of the complex between the chaperone and survivin, resulted in induction of autophagy in glioblastoma cells and suppression of tumor growth in mice model (immunocompromised CB17 SCID/beige female mice), as well as longer survival [ 99 ]. Moreover, inhibition of Hsp90 in glioblastoma cancer stem cell-like cells (T98G) increased their sensitization to the radiotherapy [ 100 ]. Clearly, inhibition of Hsp90 has shown a positive effect on survival in vivo and in vitro [ 101 , 102 ].…”

Section: Expression Of Hsps In Brain Tumorsmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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Section: Expression Of Hsps In Brain Tumorsmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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show abstract

“…The spheroids were then embedded in an embedding medium (Tissue-Tek ® O.C.T. Compound, Sakura Finetechnical Co., Ltd., Tokyo, Japan) and sliced into frozen sections 10–20 µm in thickness using a cryostat (Cryostar NX50™, Thermo Fisher Scientific Inc., Carlsbad, CA) ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

“…The human glioblastoma cell line, T98G (JCRB, Tokyo, Japan), was used in this study. T98G cells were cultured in α-minimum essential medium (α-MEM) supplemented with 20 mM 4-(2hydroxyethyl) piperazine ethane sulfonic acid, 8 mM NaHCO 3 , 50 μg/ml streptomycin, 50 U/ml penicillin, and 10% fetal bovine serum, and maintained in a humidified incubator at 37°C under conditions of 98% air and 2% CO 2 (23)(24)(25).…”

Section: Cell Culturementioning

confidence: 99%

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients

et al. 2023

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This study conducted fundamental research to develop a more effective BNCT targeting cancer stem cells. We constructed plasmids that induced the overexpression of L-type amino acid transporter 1 (LAT1) tagged with tdTomato on the cytoplasmic membranes of CD133 expressing cancer cells. After transfection of the plasmids into a glioblastoma cell line (T98G), several clones overexpressing LAT1-tdTomato in the hypoxic microenvironment of the spheroids formed from each clone were obtained. Confocal laser microscopic observation confirmed that signals from LAT1-tdTomato overlapped with immunofluorescence signals from the second antibody binding to CD133 in the hypoxic microenvironment of the spheroids. As CD133-positive cells in the hypoxic microenvironment of T98G spheroids have cancer stem cell characteristics, LAT1 seems to be selectively overexpressed in cancer stem cell-like cells. An RI tracer method showed that cells overexpressing LAT1-tdTomato in the hypoxic microenvironment of spheroids incorporate 14C-BPA much more than cells that do not overexpress LAT1-tdTomato. Neutron radiation experiments showed a more significant regression in spheroids formed with clones than in spheroids formed with parental cells when spheroids were treated with 10BPA. These results suggest that BNCT combined with gene therapy targeting cancer stem cells is more effective in glioblastoma therapy.

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“…Inhibitors of Hsp90 (e.g., geldanamycin, 17DMAG, radicicol) have been shown to enhance the radiosensitivity of various cell lines ( Table 1 ) [ 161 , 162 ]. Tani and colleagues found N -vinylpyrrolidone (NVP)-AUY922 enhanced radiosensitivity in CD133-positive GBM cells [ 163 ].…”

Section: Recent Preclinical Studiesmentioning

confidence: 99%

Small Molecules and Immunotherapy Agents for Enhancing Radiotherapy in Glioblastoma

et al. 2022

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Glioblastoma (GBM) is an aggressive primary brain tumor that is associated with a poor prognosis and quality of life. The standard of care has changed minimally over the past two decades and currently consists of surgery followed by radiotherapy (RT), concomitant and adjuvant temozolomide, and tumor treating fields (TTF). Factors such as tumor hypoxia and the presence of glioma stem cells contribute to the radioresistant nature of GBM. In this review, we discuss the current treatment modalities, mechanisms of radioresistance, and studies that have evaluated promising radiosensitizers. Specifically, we highlight small molecules and immunotherapy agents that have been studied in conjunction with RT in clinical trials. Recent preclinical studies involving GBM radiosensitizers are also discussed.

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Preferential radiosensitization to glioblastoma cancer stem cell‑like cells by a Hsp90 inhibitor, N‑vinylpyrrolidone‑AUY922

Cited by 4 publications

References 31 publications

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients

Small Molecules and Immunotherapy Agents for Enhancing Radiotherapy in Glioblastoma

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