Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors

Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mehdipour, Parvin

doi:10.1007/s12032-009-9412-8

Cited by 29 publications

(21 citation statements)

References 52 publications

(51 reference statements)

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“…In addition, previous studies have confirmed that tumor suppressor gene p53 plays a critical role in the regulation of its downstream genes and cell cycle progression (25). Accordingly, we further investigated p53 protein expression and cell cycle-related biomarkers including p21, Cdc25A, Cdc2, and P-Cdc2.…”

Section: Dp Induces Cell Cycle Arrest In Glioma Cellsmentioning

confidence: 89%

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: Dp Induces Cell Cycle Arrest In Glioma Cellsmentioning

confidence: 89%

Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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“…By considering the importance of protein-and mRNA-expression of ATM gene in brain tumors [15,20], and due to the common involvement of the D1853N polymorphism of ATM gene in brain tumors [15,20], expression assay might be also included as part of the complementary investigation in the patients affected with primary breast cancer in the future studies as well.…”

Section: Discussionmentioning

confidence: 99%

Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

et al. 2010

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The involvement of ATM gene and specifically, the important role of D1853N polymorphism, as a three-hit hypothesis has been previously reported in an Iranian proband affected with brain tumor and this polymorphism could be screened in her relatives as well. The aim of present study was to investigate the involvement of D1853N polymorphism as a predisposition factor in 129 Iranian patients affected with primary breast cancer and 248 sex- and age-matched healthy controls. Mutant allele-specific PCR amplification (MASA) assay was performed to analyze the D1853N polymorphism in the ATM gene. The frequency of D1853N polymorphism in cases, internal and external controls was 31.0% (40/129), 26.9% (28/104) and 12.5% (18/144), respectively. The frequency of D1853N in total control groups, including normal external control and pedigree internal control, was 18.6% (46/248). The odds ratio was calculated with the logistic regression test, with an estimated relative risk of 2.579 (P=0.005). The significant difference was observed between the patient-carriers of this alteration and external controls (P=0.001). The number of controls harboring D1853N polymorphism was higher in internal control compared to external controls, and the difference was statistically significant (P=0.004). The significant difference was observed between the patient-carriers and external controls and could be considered as a predisposing and diagnostic marker in the population and specifically in the cancer-prone pedigrees.

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“…Previous studies have suggested that the p53 gene serves an important role in the regulation of cell cycle progression (15)(16)(17). Therefore, the protein expression levels of p53 and its downstream target gene p21, as well as CDK2, cyclin A and cyclin E cell cycle mediators were investigated following exposure of eosinophils to 0, 80 or 160 µM resveratrol for 48 h. Western blot analysis demonstrated that the protein expression levels of p53 (P=0.0378; P=0.0085), and p21 (P=0.0327; P= 0.0054) were significantly increased following treatment with 80 and 160 µM resveratrol when compared with untreated controls (Fig.…”

Section: Resveratrol Induces Cell Cycle Arrest In Eosinophilsmentioning

confidence: 99%

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

Hu¹,

Wang²,

Xia³

et al. 2016

Molecular Medicine Reports

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Abstract. Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit-8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double-staining. The protein expression levels of p53, p21, cyclin-dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration-and time-dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G 1 /S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl-2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

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Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors

Cited by 29 publications

References 52 publications

Dracorhodin perchlorate induces the apoptosis of glioma cells

Dracorhodin perchlorate induces the apoptosis of glioma cells

Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

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