Oncotarget

Research Papers:

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

Giseli Mitsuy Kayahara, Vitor Bonetti Valente, Rosani Belzunces Pereira, Felipe Yudi Kabeya Lopes, Marcelo Macedo Crivelini, Glauco Issamu Miyahara, Éder Ricardo Biasoli, Sandra Helena Penha Oliveira and Daniel Galera Bernabé _

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Oncotarget. 2020; 11:1816-1831. https://doi.org/10.18632/oncotarget.27551

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Abstract

Giseli Mitsuy Kayahara1,2, Vitor Bonetti Valente1, Rosani Belzunces Pereira1, Felipe Yudi Kabeya Lopes1, Marcelo Macedo Crivelini2, Glauco Issamu Miyahara1,2, Éder Ricardo Biasoli1,2, Sandra Helena Penha Oliveira1,3 and Daniel Galera Bernabé1,2

1 Psychoneuroimmunology Laboratory, Psychosomatic Research Center, Oral Oncology Center, São Paulo State University (Unesp), School of Dentistry, SP 15050-015, Araçatuba, São Paulo, Brazil

2 Department of Diagnosis and Surgery, São Paulo State University (Unesp), School of Dentistry, SP 15050-015, Araçatuba, São Paulo, Brazil

3 Laboratory of Immunopharmacology, Department of Basic Sciences, São Paulo State University (Unesp), School of Dentistry, SP 15050-015, Araçatuba, São Paulo, Brazil

Correspondence to:

Daniel Galera Bernabé,email: [email protected]

Keywords: melatonin; cancer; oral cancer; carcinogenesis; pineal gland

Received: September 10, 2019     Accepted: March 14, 2020     Published: May 19, 2020

ABSTRACT

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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