Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma

Autor(es)

Chuffa, Luiz Gustavo A. ^[1] ; Alves, Michelly S. ^[1] ; Martinez, Marcelo ^[2] ; Camargo, Isabel Cristina C. ^[3] ; Pinheiro, Patricia F. F. ^[1] ; Domeniconi, Raquel F. ^[1] ; Junior, Luiz Antonio L. ^[1] ; Martinez, Francisco Eduardo ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Univ Estadual Paulista, Dept Anat, Inst Biosci Botucatu, BR-510 Sao Paulo - Brazil

^[2] UFSCar Univ Fed Sao Carlos, Dept Morphol & Pathol, BR-13565905 Sao Paulo - Brazil

^[3] UNESP Univ Estadual Paulista, Fac Sci & Letters, Dept Biol Sci, BR-19806900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Endocrine-Related Cancer; v. 23, n. 2, p. 65-76, FEB 2016.
• Citações Web of Science: 23

Resumo

Apoptosis plays an important role in the treatment of cancer, and targeting apoptosis-related molecules in ovarian cancer (OC) is of great therapeutic value. Melatonin (Mel) is an indoleamine displaying several anti-cancer properties and has been reported to modulate apoptosis signaling in multiple tumor subtypes. We investigated OC and the role of Mel therapy on the pro-apoptotic (p53, BAX, caspase-3, and cleaved caspase-3) and anti-apoptotic (Bcl-2 and survivin) proteins in an ethanol (EtOH)-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 mu g 7,12-dimethylbenz(a) anthracene dissolved in 10 mu l of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 mu g/100 g BW per day) for 60 days. Body weight gain, EtOH consumption, and energy intake were unaffected by the treatments. Interestingly, absolute and relative OC masses showed a significant reduction after Mel therapy, regardless of EtOH consumption. To accomplish OC-related apoptosis, we first observed that p53, BAX, caspase-3, and cleaved caspase-3 were downregulated in OC tissue while Bcl-2 and survivin were overexpressed. Notably, Mel therapy and EtOH intake promoted apoptosis along with the upregulation of p53, BAX, and cleaved caspase-3. Fragmentation of DNA observed by TUNEL-positive nuclei was also enhanced following Mel treatment. In addition, Bcl-2 was downregulated by the EtOH intake and lower survivin levels were observed after Mel therapy. Taken together, these results suggest that Mel induce apoptosis in OC cells of EtOH-preferring animals. (AU)

• Processo FAPESP: 14/05196-3 - Indução tumoral ovariana e influência da terapia com melatonina sobre a apoptose em ratas UChB
• Beneficiário: Michelly da Silva Alves
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/02466-7 - Indução tumoral ovariana e influência da melatonina sobre o processo inflamatório via sinalização mediada pelo receptor Toll-like 4 em ratas UChB
• Beneficiário: Luiz Gustavo de Almeida Chuffa
• Modalidade de apoio: Auxílio à Pesquisa - Regular