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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Franco, Daiane G. [1] ; Moretti, Isabele F. [1] ; Marie, Suely K. N. [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Fac Med FMUSP, BR-01246903 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Molecules; v. 23, n. 5 MAY 2018.
Web of Science Citations: 7
Abstract

The disruption of mitochondrial activity has been associated with cancer development because it contributes to regulating apoptosis and is the main source of reactive oxygen species (ROS) production. Mitochondrial transcription factor A (TFAM) is a protein that maintains mitochondrial DNA (mtDNA) integrity, and alterations in its expression are associated with mitochondrial damage and cancer development. In addition, studies have shown that mitochondria are a known target of melatonin, the pineal gland hormone that plays an important anti-tumorigenic role. Thus, we hypothesized that melatonin decreases the expression of TFAM (RNA and protein) in the human glioblastoma cell line U87MG, which disrupts mtDNA expression and results in cell death due to increased ROS production and mitochondrial damage. Our results confirm the hypothesis, and also show that melatonin reduced the expression of other mitochondrial transcription factors mRNA (TFB1M and TFB2M) and interfered with mtDNA transcription. Moreover, melatonin delayed cell cycle progression and potentiated the reduction of cell survival due to treatment with the chemotherapeutic agent temozolomide. In conclusion, elucidating the effect of melatonin on TFAM expression should help to understand the signaling pathways involved in glioblastoma progression, and melatonin could be potentially applied in the treatment of this type of brain tumor. (AU)

FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
Grantee:Berenice Bilharinho de Mendonça
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 14/17220-6 - Melatonin effects on glial tumors mitochondrial activity
Grantee:Daiane Gil Franco
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
Grantee:Suely Kazue Nagahashi Marie
Support Opportunities: Research Projects - Thematic Grants