Abstract Title:

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

Abstract Source:

Endocr Relat Cancer. 2015 Nov 10. Epub 2015 Nov 10. PMID: 26555801

Abstract Author(s):

Luiz Gustavo de Almeida Chuffa, Michelly da Silva Alves, Marcelo Martinez, Isabel Camargo, Patricia Pinheiro, Raquel Domeniconi, Luiz Antonio Lupi Júnior, Francisco Martinez

Article Affiliation:

Luiz Gustavo de Almeida Chuffa


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 anticancer 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 100µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL 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 µg/100 g b.w./day) for 60 days. Body weight gain, EtOH consumption and energyintake 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.

Study Type : Animal Study

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