Mitochondria Transcription Factor A: A Putative Target for the Effect of Melatonin on U87MG Malignant Glioma Cell Line

Franco, Daiane Gil; Moretti, Isabele Fattori; Marie, Suely Kazue Nagahashi

doi:10.3390/molecules23051129

Cited by 36 publications

(35 citation statements)

References 71 publications

(99 reference statements)

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“…Mitochondria are the main source of reactive oxygen species (ROS) production and are a known target of melatonin [61,62]. As previously reported, melatonin presented a pro-oxidant effect in cancer cells [34][35][36]. A high concentration of ROS can damage mitochondrial and nuclear DNA and modify the expression of oncogenes and tumor suppressor genes [63,64].…”

Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 90%

“…The antioxidant activity of melatonin is observed through the prevention of free radical formation, as well as the capacity to upregulate antioxidant enzyme activity and downregulate pro-oxidant enzymes [31][32][33]. Furthermore, in cancer cells, melatonin presents a paradoxical pro-oxidant effect, leading to cell death [34][35][36]. Therefore, melatonin may inhibit cancer development by increasing the induction of oxidative stress in tumor cells [37].…”

Section: Melatoninmentioning

confidence: 99%

“…A high concentration of ROS can damage mitochondrial and nuclear DNA and modify the expression of oncogenes and tumor suppressor genes [63,64]. In the hopes of blocking tumor growth, Franco et al [35] studied the effects of 3 mM melatonin on human GBM cells and observed a reduced expression of mitochondrial transcription factor A (TFAM), which is an essential protein that maintains mitochondrial DNA (mtDNA) integrity [65,66]. Moreover, melatonin selectively induced a surprisingly concentration-dependent increase in ROS production and delayed cell-cycle progression in GBM cancer cells as compared to the control group [35], while the presence of high levels of mitochondria-synthesized melatonin appears to be toxic for GBM and GSCs [67].…”

Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 99%

“…In the hopes of blocking tumor growth, Franco et al [35] studied the effects of 3 mM melatonin on human GBM cells and observed a reduced expression of mitochondrial transcription factor A (TFAM), which is an essential protein that maintains mitochondrial DNA (mtDNA) integrity [65,66]. Moreover, melatonin selectively induced a surprisingly concentration-dependent increase in ROS production and delayed cell-cycle progression in GBM cancer cells as compared to the control group [35], while the presence of high levels of mitochondria-synthesized melatonin appears to be toxic for GBM and GSCs [67]. This effect of melatonin on ROS production may be due to the altered expression of respiratory chain genes, which could depend on the activity of the transcription factors TFAM, TFB1M, and TFB2M [35].…”

Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 99%

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Melatonin’s Antineoplastic Potential Against Glioblastoma

Moretti

Favero

Rodella

et al. 2020

Cells

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Glioblastoma (GBM) is one of the most intransigent and aggressive brain tumors, and its treatment is extremely challenging and ineffective. To improve patients’ expectancy and quality of life, new therapeutic approaches were investigated. Melatonin is an endogenous indoleamine with an incredible variety of properties. Due to evidence demonstrating melatonin’s activity against several cancer hallmarks, there is growing interest in its use for preventing and treating cancer. In this review, we report on the potential effects of melatonin, alone or in combination with anticancer drugs, against GBM. We also summarize melatonin targets and/or the intracellular pathways involved. Moreover, we describe melatonin’s epigenetic activity responsible for its antineoplastic effects. To date, there are too few clinical studies (involving a small number of patients) investigating the antineoplastic effects of melatonin against GBM. Nevertheless, these studies described improvement of GBM patients’ quality of life and did not show significant adverse effects. In this review, we also report on studies regarding melatonin-like molecules with the tumor-suppressive properties of melatonin together with implemented pharmacokinetics. Melatonin effects and mechanisms of action against GBM require more research attention due to the unquestionably high potential of this multitasking indoleamine in clinical practice.

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Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 90%

Section: Melatoninmentioning

confidence: 99%

Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 99%

Section: In Vitro Evidence Of Melatonin Effects Against Glioblastomamentioning

confidence: 99%

See 2 more Smart Citations

Melatonin’s Antineoplastic Potential Against Glioblastoma

Moretti

Favero

Rodella

et al. 2020

Cells

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show abstract

“…This indolamine, due to its apoptotic effects, can have synergistic effects with anti‐tumor medications and enhance their tumor cytotoxicity . It can also reduce side effects . Changes in signaling pathways and high expression of oncogenes and inhibition of tumor suppressor genes can disrupt normal cellular activity and cause neoplastic changes .…”

Section: Introductionmentioning

confidence: 99%

The effects of melatonin on signaling pathways and molecules involved in glioma

Neamati

Asemi

2019

Fundamemntal Clinical Pharma

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Glioblastoma is one of the most common brain tumors with high invasion and malignancy. Despite extensive research in this area and the use of new and advanced therapies, the survival rate in this disease is very low. In addition, resistance to treatment has also been observed in this disease. One of the reasons for rapid progression and failure in treatment for this disease is the presence of a class of cells with high proliferation and high differentiation, a class called glioblastoma stem‐like cells shown as being the source of glioblastoma tumors. It has been reported that several oncogenes are expressed in this disease. One important issue in recognizing the pathogenesis of this disease, and which could improve the treatment process, is the identification of involved oncogenes as well as molecules that affect the reduction of the expression of these oncogenes. Melatonin regulates the biological rhythm and inhibits the proliferation of malignant glioma cells due to antioxidant and anti‐apoptotic effects. Melatonin has been considered in biological processes and in signaling pathways involved in the development of glioma. The aim of this review is to investigate the effects of melatonin on signaling pathways and molecules involved in the progression of glioma.

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High expression of ALDH1A3 might independently influence poor progression‐free and overall survival in patients with glioma via maintaining glucose uptake and lactate production

Xia

Lin

et al. 2019

Cell Biology International

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Recent studies have found that the acetaldehyde dehydrogenase 1A3 (ALDH1A3) gene is a marker of glioma stem cells. A total of 115 brain glioma specimens were collected and classified into grade I–IV, while non‐tumor brain tissue specimens, taken from 12 patients of vascular malformation surgery, were used as control. ALDH1A3 gene promoter methylation in glioma tissues was detected by pyrosequencing, while immunohistochemistry and western blot were used to detect ALDH1A3 protein expressions in different grades of glioma tissues and normal brain tissues. The expression of ALDH1A3 in the glioma cell line U87 was detected by quantitative real‐time polymerase chain reaction and RNA‐Seq technology was applied to investigate differentially expressed genes before and after silencing the ALDH1A3 gene. Among the 115 glioma tissue specimens, 50 (43.48%) showed low and 65 (56.52%) high expression of ALDH1A3, but no expression was detected in the control. Univariate and multivariate COX regression analyses showed that the patient's tumor pathological grade, the methylation status of ALDH1A3 promoter, and the expression of ALDH1A3 protein were risk factors for progression‐free survival (PFS) and overall survival (OS) (all P < 0.05) and the OS of mice with silenced ALDH1A3 in a glioma nude mouse model was prolonged. U87 experiments revealed that ALDH1A3 expression had significant effects on apoptosis, proliferation, cell cycle, mitochondrial membrane potential, glucose consumption, lactate production, invasion ability, and expression of the pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) in glioma cells. ALDH1A3 protein expression is a marker for poor PFS and OS in glioma patients.

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Mitochondria Transcription Factor A: A Putative Target for the Effect of Melatonin on U87MG Malignant Glioma Cell Line

Cited by 36 publications

References 71 publications

Melatonin’s Antineoplastic Potential Against Glioblastoma

Melatonin’s Antineoplastic Potential Against Glioblastoma

The effects of melatonin on signaling pathways and molecules involved in glioma

High expression of ALDH1A3 might independently influence poor progression‐free and overall survival in patients with glioma via maintaining glucose uptake and lactate production

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