Can hsp90α-Targeted siRNA Combined With TMZ Be a Future Therapy for Glioma?

Cruickshanks, Nichola; Shervington, Leroy Alexander; Patel, Rahima; Munje, Chinmay; Thakkar, Dipti; Shervington, Amal

doi:10.3109/07357901003630967

Cited by 20 publications

(28 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each protein band was normalized to the expression level of β-actin used as loading control, and the ratios are given by the numbers combined siRNA and drug treatment reduced the viability as did drug treatment alone. In contrast, combined siRNA against Hsp90α and temozolomide treatment led to a more pronounced reduction of viability of U87-MG glioma cells compared with drug treatment alone [4], which suggests that the effect of Hsp90α knock down might depend on cell line and drug used.…”

Section: Discussionmentioning

confidence: 52%

“…SiRNA-mediated knockdown of several promising targets for cancer treatment (osteopontin, survivin, HIF-1α, aurora-A, Akt) has been already shown in the literature [7,14,17,19,20]. For example, the combination of siRNA against Hsp90α and temozolomide enhanced the sensitivity of glioma cells to this drug, suggesting a promising alternative treatment to chemotherapy alone [4]. In addition, clinical studies using this novel approach for cancer therapy have been already initiated [9].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α

et al. 2012

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α

et al. 2012

View full text Add to dashboard Cite

show abstract

“…28 Furthermore, HSP90-α has therapeutic implications since both HSP90-α gene silencing and protein inhibitor approaches resulted in a dramatic reduction in cell viability of gliomas. 6,27 Alvespimycin (17-DMAG), an HSP90 inhibitor, is currently in clinical trials for several tumors with favorable results. 14,18 In studying MBs, Ayrault et al reported that, in order for 17-DMAG to exert its antitumorigenic effect, an intact p53 response is required.…”

mentioning

confidence: 99%

Expression of heat shock proteins in medulloblastoma

Alexiou

Vartholomatos

Stefanaki

et al. 2013

PED

View full text Add to dashboard Cite

Object Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis. Methods The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed. Results Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076). Conclusions A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.

show abstract

“…RNAi with non-enzymatic targets was also observed to be valuable in sensitizing cells to TMZ: In a previous study, it was noted that silencing the voltage-gated potassium channel Eag1 makes glioblastoma cells more vulnerable to TMZ (71). The same effect occurred for drug resistance proteins, heat-shock proteins 90, 27 and 72, and other targets involved in cell signaling (72)(73)(74)(75)(76)(77).…”

Section: Discussionmentioning

confidence: 98%

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

Resende

Titze‐de‐Almeida

2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.

show abstract

Can hsp90α-Targeted siRNA Combined With TMZ Be a Future Therapy for Glioma?

Cited by 20 publications

References 24 publications

Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α

Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α

Expression of heat shock proteins in medulloblastoma

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

Contact Info

Product

Resources

About