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

Autor(es)

Franco, Daiane G. ^[1] ; Moretti, Isabele F. ^[1] ; Marie, Suely K. N. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med FMUSP, BR-01246903 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 23, n. 5 MAY 2018.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/17220-6 - Efeitos da melatonina na atividade mitocondrial de tumores gliais
• Beneficiário: Daiane Gil Franco
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Temático