Ação da melatonina na modulação do câncer de colo de útero
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Data
2021-09-10
Autores
Frigieri, Barbara Maria
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma de colo de útero, também chamado de câncer cervical, é o segundo tipo de neoplasia mundialmente mais frequente em mulheres. A cada ano surgem cerca de 530 mil novos casos, sendo a quarta causa de morte em países em desenvolvimento, com aproximadamente 275 mil mortes por ano. O tratamento para câncer de colo de útero inclui cirurgia, terapia por irradiação e quimioterapia, mas por serem métodos invasivos, pesquisadores têm buscado novos fármacos antitumorais para auxiliar a eficiência dos tratamentos. A melatonina seria um desses fármacos, pois tem atividade antitumoral por meio de vários mecanismos, incluindo seus efeitos antiproliferativos e pró-apoptóticos, bem como sua potente ação pró-oxidante em células tumorais. Melatonina é um hormônio natural produzido pela glândula pineal, regula o ritmo circadiano, possuindo propriedades imunomoduladoras, anti-inflamatórias e anti-oxidantes. Em função da importância da melatonina, foi proposto o presente trabalho que teve como objetivo geral avaliar seu potencial efeito nas células neoplásicas sobre a morfologia, proliferação e migração celular, citotoxicidade, genotoxicidade, apoptose, ciclo celular e expressão gênica, observando como ocorre essa ação e como essas alterações podem participar do processo tumorigênico. Foram utilizadas duas linhagens tumorigênicas, uma de carcinoma de colo de útero (SiHa) e outra de adenocarcinoma de colo de útero (HeLa), além de uma linhagem de células não tumorigênicas, derivada de células de queratinócitos da pele humana (HaCaT), tratadas com melatonina (concentração de 100nM e 1mM) por 4, 24, 48 e 72 horas. Nós observamos que a melatonina não alterou a morfologia celular, mas reduziu a proliferação e migração celular, não foi citotóxica, mas foi genotóxica, reduziu formação de colônias tumorais, induziu o processo de apoptose inicial, tardia e necrose e estimulou as células a estacionarem nas fases G1/G0 e G2/M do ciclo celular. Além disso, observamos que a melatonina também modulou a via gênica PI3K/AKT, pela ativação dos receptores MTNR1A e MTNR1B e diminuição de AKT. Dessa maneira, a melatonina parece apresentar uma ação antitumorigênica, por mecanismos relacionados às vias antiproliferativas, antimigratórias e apoptóticas, e abrem novas possibilidades de estudos futuros para terapias associadas ao câncer de colo de útero.
Cervical cancer, also called cervical cancer, is the second most common type of cancer in women worldwide. Each year there are about 530 thousand new cases, being the fourth leading cause of death in developing countries, with approximately 275,000 deaths per year. Approximately 35% of women diagnosed with cervical carcinoma have recurrent disease, with 90% of these findings within three years of initial treatment. Treatment for cervical cancer includes surgery, radiation therapy and chemotherapy, but because they are invasive methods, researchers have been looking for new anti-tumor drugs to help with the efficiency of treatments. Melatonin would be one of these drugs, as it has antitumor activity through several mechanisms, including its antiproliferative and pro-apoptotic effects, as well as its potent pro-oxidant action on tumor cells. Melatonin is a natural hormone produced by the pineal gland, regulates the circadian rhythm, having immunomodulatory, anti-inflammatory and anti-oxidant properties. It not only regulates biological functions, but is important in the actions of pathological processes, including cancer. Due to the importance of melatonin, the present work was proposed, which aimed to evaluate its potential effect on neoplastic cells on cell morphology, proliferation and migration, cytotoxicity, genotoxicity, apoptosis and cell cycle, gene and protein expression, observing how it occurs this action and how these changes can participate in the tumorigenic process. In the present work we observed that melatonin did not change cell morphology, but reduced cell proliferation and migration, was not cytotoxic, but genotoxic, reduced tumor colony formation, induced the process of early, late and necrosis apoptosis and stimulated cells to park in the G1/G0 and G2/M phases of the cell cycle. Thus, melatonin seems to have an anti-tumorigenic action, through mechanisms related to anti-proliferative, anti-migratory and apoptotic pathways, opening new possibilities for future studies for therapies associated with cervical cancer.
Cervical cancer, also called cervical cancer, is the second most common type of cancer in women worldwide. Each year there are about 530 thousand new cases, being the fourth leading cause of death in developing countries, with approximately 275,000 deaths per year. Approximately 35% of women diagnosed with cervical carcinoma have recurrent disease, with 90% of these findings within three years of initial treatment. Treatment for cervical cancer includes surgery, radiation therapy and chemotherapy, but because they are invasive methods, researchers have been looking for new anti-tumor drugs to help with the efficiency of treatments. Melatonin would be one of these drugs, as it has antitumor activity through several mechanisms, including its antiproliferative and pro-apoptotic effects, as well as its potent pro-oxidant action on tumor cells. Melatonin is a natural hormone produced by the pineal gland, regulates the circadian rhythm, having immunomodulatory, anti-inflammatory and anti-oxidant properties. It not only regulates biological functions, but is important in the actions of pathological processes, including cancer. Due to the importance of melatonin, the present work was proposed, which aimed to evaluate its potential effect on neoplastic cells on cell morphology, proliferation and migration, cytotoxicity, genotoxicity, apoptosis and cell cycle, gene and protein expression, observing how it occurs this action and how these changes can participate in the tumorigenic process. In the present work we observed that melatonin did not change cell morphology, but reduced cell proliferation and migration, was not cytotoxic, but genotoxic, reduced tumor colony formation, induced the process of early, late and necrosis apoptosis and stimulated cells to park in the G1/G0 and G2/M phases of the cell cycle. Thus, melatonin seems to have an anti-tumorigenic action, through mechanisms related to anti-proliferative, anti-migratory and apoptotic pathways, opening new possibilities for future studies for therapies associated with cervical cancer.
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Palavras-chave
Cultura celular, Anti-proliferação, Gene AKT, Cell culture, Anti-proliferative, AKT gene