Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Luiz Gustavo De Almeida Chuffa
* ORCID logo ,
Yohan Ricci Zonta
,
Marcelo Martinez
,
Isabel Cristina Cherici Camargo
,
Raquel Fantin Domeniconi
,
Luiz Antonio Lupi Junior
,
Patricia Fernanda Felipe Pinheiro
,
Russel J. Reiter
,
Francisco Eduardo Martinez
Version 1 : Received: 3 March 2017 / Approved: 6 March 2017 / Online: 6 March 2017 (06:34:02 CET)

A peer-reviewed article of this Preprint also exists.

Zonta, Y.R.; Martinez, M.; Camargo, I.C.C.; Domeniconi, R.F.; Lupi Júnior, L.A.; Pinheiro, P.F.F.; Reiter, R.J.; Martinez, F.E.; Chuffa, L.G.A. Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats. Int. J. Mol. Sci. 2017, 18, 763. Zonta, Y.R.; Martinez, M.; Camargo, I.C.C.; Domeniconi, R.F.; Lupi Júnior, L.A.; Pinheiro, P.F.F.; Reiter, R.J.; Martinez, F.E.; Chuffa, L.G.A. Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats. Int. J. Mol. Sci. 2017, 18, 763.

Abstract

Angiogenesis is a hallmark of ovarian cancer (OC) it promotes rapid cell growth and the associated metastasis. Identifying new bioactive compounds to target angiogenesis may provide valuable paradigms as therapeutic strategies. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received i.p. injections of melatonin (200 µg/100 g body weight/day) for 60 days. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1R was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFB1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC of an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.

Keywords

ovarian cancer; melatonin; angiogenesis; VEGF; VEGFR; HIF-1α

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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