Pineal gland protects against chemically induced oral carcinogenesis and inhibits tumor progression in rats

Clinical investigations suggest that melatonin suppression and circadian dysfunction may be related to cancer development in shift workers. Studies also show that melatonin suppression after pinealectomy increases cancer incidence in preclinical models. However, no study evaluated the influence of p...

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Bibliographic Details
Authors: Kayahara, Giseli Mitsuy [UNESP], Valente, Vitor Bonetti [UNESP], Pereira, Rosani Belzunces [UNESP], Lopes, Felipe Yudi Kabeya [UNESP], Crivelini, Marcelo Macedo [UNESP], Miyahara, Glauco Issamu [UNESP], Biasoli, Éder Ricardo [UNESP], Oliveira, Sandra Helena Penha de [UNESP], Bernabé, Daniel Galera [UNESP]
Format: article
Status:Published version
Publication Date:2020
Country:Brasil
Institution:Universidade Estadual Paulista (UNESP)
Repository:Repositório Institucional da UNESP
Language:English
OAI Identifier:oai:repositorio.unesp.br:11449/200585
Online Access:http://dx.doi.org/10.18632/oncotarget.27551
http://hdl.handle.net/11449/200585
Access Level:Open access
Keyword:Cancer
Carcinogenesis
Melatonin
Oral cancer
Pineal gland
Description
Summary:Clinical investigations suggest that melatonin suppression and circadian dysfunction may be related to cancer development in shift workers. Studies also show that melatonin suppression after pinealectomy increases cancer incidence in preclinical models. However, no study evaluated the influence of pinealectomy on oral cancer development. In the current study, we investigated the effects of pinealectomy on oral squamous cell carcinoma (OSCC) occurrence and progression in rats. Rats submitted to sham surgery were used as control. Pinealectomy promoted an increase of 140% in OSCC occurrence when compared to sham animals. Tumors from pinealectomized rats displayed a higher volume and thickness than the tumors from sham-operated animals. Pinealectomy induced atrophy of the epithelium adjacent to the oral lesions. Pinealectomized rats showed higher mean number of tumor-associated macrophages and eosinophils in the invasive front of OSCC. In addition, nuclear overexpression of ERK1/2 and p53 was also observed in the front of carcinomas from pinealectomized rats. These results reveal that pineal gland plays a protective role against oral carcinogenesis. The melatonin suppression caused by the pinealectomy might contribute to oral cancer development by acting on ERK1/2 and p53 pathways and regulating tumor inflammation.

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