Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xing; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

doi:10.1186/1748-717x-8-195

Cited by 33 publications

(22 citation statements)

References 29 publications

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“…The effect of Dp treatment on the proliferation of U87MG and T98G cells was determined by MTT assay. Briefly, the cells were seeded in 96-well plates at a density of 1x10 4 cells/well in a final volume of 150 µl of culture medium with 10% FBS. After 24 h of incubation, Dp at various concentrations (0, 10, 20, 40, 80, and 160 µM) was added to each well for 24, 48 and 72 h. Subsequently, 20 µl of MTT (5 mg/ml solution in 1X phosphate-buffered saline) was added to each well for a 4-h incubation at 37˚C.…”

Section: Methodsmentioning

confidence: 99%

“…Although current treatment has modestly improved patient survival, patients with gliomas still have a very poor prognosis and low cure rates. It was reported that patients with anaplastic astrocytoma have a median survival of 2-3 years, but for those with more aggressive glioblastomas, the median survival is only 12-15 months (4,5). Currently, surgery is considered as an important initial clinical approach for glioma, yet it is difficult to completely remove diffuse tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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Abstract. Dracorhodin perchlorate (Dp), a synthetic analogue of the antimicrobial anthocyanin red pigment, has recently been shown to induce apoptotic cell death in various types of cancer cells. Yet, the inhibitory effect of Dp on human glioma cells remains uninvestigated. Therefore, in the present study, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and cell cycle progression in glioma U87MG and T98G cells, respectively. Annexin V-FITC/propidium iodide double staining and JC-1 staining were separately applied to determine cellular apoptosis and mitochondrial membrane potential damage in the cells. The expression levels of associated proteins involved in cell cycle progression and apoptosis were measured by western blotting. The activities of caspase-9/-3 were determined by Caspase-Glo-9/3 assay. The results indicated that Dp treatment significantly inhibited cell proliferation in a dose-and time-dependent manner, and blocked cell cycle progression at the G 1 /S phase in the U87MG and T98G cells via the upregulation of p53 and p21 protein expression, and simultaneous downregulation of Cdc25A, Cdc2 and P-Cdc2 protein expression. Additionally, Dp treatment led to the loss of cellular mitochondrial membrane potential, and the release of cytochrome c, and strongly induced the occurence of apoptosis. Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/-3 were activated and their activities were elevated after Dp treatment. These findings indicate that Dp inhibits cell proliferation, induces cell cycle arrest and apoptosis in glioma cells, and is a possible candidate for glioma treatment. IntroductionBrain glioma is the most common form of neural malignancy in the nervous system. High grade glioma is the leading cause of brain cancer-related mortality due to its high invasive ability and malignant proliferation (1,2). Glioma incidence accounts for approximately 40-50% of all intracranial tumors (3). Although current treatment has modestly improved patient survival, patients with gliomas still have a very poor prognosis and low cure rates. It was reported that patients with anaplastic astrocytoma have a median survival of 2-3 years, but for those with more aggressive glioblastomas, the median survival is only 12-15 months (4,5). Currently, surgery is considered as an important initial clinical approach for glioma, yet it is difficult to completely remove diffuse tumor cells. Radiotherapy and chemotherapy after initial surgical resection are regarded as an effective therapeutic plan to prevent disease recurrence (6). However, most attempts to increase the efficacy of radiotherapy and chemotherapy are hampered by unacceptable late toxicities (7). In addition, the drug-resistance of tumor cells finally results in the abrogation of the effects of current chemotherapeutic agents (8). Accordingly, to improve the prognosis and quality of life of patients with gliomas, the ...

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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“…In melanoma, BPA accumulation and the melanin-producing activity of the tumor cells are correlated because BPA is a tyrosine analogue, a precursor of melanin [25]. Optimization of some experimental methods, such as targeting molecules overexpressed on the tumor surface, preloading compounds, increasing total dose, extending infusion time, and changing the route of administration, could increase tumor boron uptake and/or the ratio of the tumor-to-blood and tumor-to-normal tissue, to improve treatment efficacy [26]. Although the absolute amount of boron in our research was not sufficient to kill the cells with neutron irradiation, the ratios of the boron tumor/blood and tumor/normal tissue were both more than 2.5 : 1.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of pathology and boronophenylalanine uptake in experimental orthotopic and heterotopic amelanotic melanoma

Sun¹,

Li²,

Wu³

et al. 2014

Melanoma Research

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Pathobiologic characteristics of cerebral and cutaneous melanoma may cause an increase in mortality resulting from brain metastases in advanced melanoma patients, in addition to anatomic lesions and biological effects caused by the tumor location. We established intracranial and subcutaneous melanoma models using cultured malignant cells derived from amelanotic melanoma. The median survival times in a mouse model with intracranial tumors was 20 days, but a mouse model with subcutaneous tumors did not show cachexia until they were killed 28 days after inoculation with tumor cells. Histopathological analysis showed that a high karyokinesis phase and nuclear pleomorphism appeared in the intracranial model compared with the subcutaneous tumor model mice. The tumor boron concentration at 2.5 h after boronophenylalanine administration was 15.21±3.88 μg/g in an intracranial melanoma xenograft and 19.85±3.63 μg/g in a subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and shorter survival time than did subcutaneous melanoma when the same number of tumor cells were injected, and subcutaneous and intracranial amelanotic malignant melanoma tumors are both fitted for boron neutron capture therapy.

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“…The cellular distribution of 10 B from L-para-boronophenylalanine-10 B (BPA) is believed to be largely dependent on the capability of the cells to take up 10 B whereas that from sodium mercaptoundecahydrododecaborate-10 B (BSH) mainly relies on drug diffusion [11]. Importantly, the use of a 10 B-carrier in BNCT, especially BPA, not only effectively eliminates hypoxia and quiescent cells but also kills oxygenated and proliferative cells [11,94].…”

Section: Application Of Bnct In Quiescent Tumor Cellsmentioning

confidence: 99%

Research progress on therapeutic targeting of quiescent cancer cells

Zhang

Gan

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Cellular quiescence (G0) is a sleep-like cellular state that allows cells to maintain the ability to re-enter and exit the proliferative cycle. Quiescent cancer cells are considered a therapeutic challenge since they are often resistant to conventional chemoradiotherapy resulting in disease progression and relapse. To date, the majority of published studies have focused on identifying molecules that target proliferating tumor cells while limited information is available on methods to target quiescent cancer cells. This review provides a summary of the relevant molecular mechanisms underlying quiescence maintenance and pharmacological interventions aimed at either eliminating this cancer cell subpopulation or indefinitely maintaining the quiescence state. Furthermore, the irradiation responses of quiescent cancer cells, in particular, the influence of manipulating intratumor hypoxia and radiation properties on radiosensitivity, are discussed. The main aim of this article is to provide a theoretical basis for the effective targeted killing of dormant tumor cells. ARTICLE HISTORY

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Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

Cited by 33 publications

References 29 publications

Dracorhodin perchlorate induces the apoptosis of glioma cells

Dracorhodin perchlorate induces the apoptosis of glioma cells

Comparative analysis of pathology and boronophenylalanine uptake in experimental orthotopic and heterotopic amelanotic melanoma

Research progress on therapeutic targeting of quiescent cancer cells

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