title: Vitamin K3 induces antiproliferative effect in cervical epithelial cells transformed by HPV 16 (SiHa cells) through the increase in reactive oxygen species production.
abstract: Cervical cancer is characterized as an important public health problem. According to latest estimates, cancer of the cervix is the fourth most common cancer among women. Due to its high prevalence, the search for new and efficient drugs to treat this infection is continuous. The progression of HPV-associated cervical cancer involves the expression of two viral proteins, E6 and E7, which are rapidly degraded by the ubiquitin-proteasome system through the increase in reactive oxygen species generation. Vitamins are essential to human substances, participate in the regulation of metabolism, and facilitate the process of energy transfer.
  
  
  
  Some early studies have indicated that vitamin K3 exerts antitumor activity by inducing cell death by apoptosis through an increase in the generation of reactive oxygen species. Thus, we evaluated the antiproliferative effect and a likely mechanism of action of vitamin K3 against cervical epithelial cells transformed by HPV 16 (SiHa cells) assessing the production of total ROS, the mitochondrial membrane potential, the cell morphology, the cell volume, and the cell membrane integrity.
  
  
  
  Our results show that vitamin K3 induces an increase in ROS production in SiHa cells, triggering biochemical and morphological events, such as depolarization of mitochondrial membrane potential and decreasing cell volume.
  
  
  
  Our data showed that vitamin K3 generates an oxidative imbalance in SiHa cells, leading to mechanisms that induce cell death by apoptosis.
authors.affiliation: Programa de Pós-graduação em Biociências Aplicadas á Farmácia, Universidade Estadual de Maringá, Av. Colombo, 5.790, 87020-900, Maringá, PR, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: de Carvalho Scharf Santana
authors.affiliation: Programa de Pós-graduação em Biociências Aplicadas á Farmácia, Universidade Estadual de Maringá, Av. Colombo, 5.790, 87020-900, Maringá, PR, Brazil.
authors.forename: Natália Alves
authors.initials: NA
authors.lastname: Lima
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av Colombo, 5.790, Maringá, PR, 87020-900, Brazil.
authors.forename: Vânia Cristina
authors.initials: VC
authors.lastname: Desoti
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av Colombo, 5.790, Maringá, PR, 87020-900, Brazil.
authors.forename: Danielle Lazarin
authors.initials: DL
authors.lastname: Bidóia
authors.affiliation: Programa de Pós-graduação em Ciências da Saúde, Universidade Estadual de Maringá, Av Colombo, 5.790, Maringá, PR, 87020-900, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: de Souza Bonfim Mendonça
authors.affiliation: Programa de Pós-graduação em Biociências Aplicadas á Farmácia, Universidade Estadual de Maringá, Av. Colombo, 5.790, 87020-900, Maringá, PR, Brazil.
authors.forename: Bianca Altrão
authors.initials: BA
authors.lastname: Ratti
authors.affiliation: Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo, 5.790, Bloco I-90, Maringá, PR, 87020-900, Brazil.
authors.forename: Tânia Ueda
authors.initials: TU
authors.lastname: Nakamura
authors.affiliation: Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo, 5.790, Bloco I-90, Maringá, PR, 87020-900, Brazil.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
authors.affiliation: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Av. Colombo, 5.790, Maringá, PR, 87020-900, Brazil.
authors.forename: Marcia Edilaine Lopes
authors.initials: ME
authors.lastname: Consolaro
authors.affiliation: Departamento de Química, Faculdade de Ciências, Universidade Estadual Paulista Júlio de Mesquita Filho, Av Eng Luiz Edmundo Carrijo Coube, S/N, Bauru, SP, 17033360, Brazil.
authors.forename: Valdecir Farias
authors.initials: VF
authors.lastname: Ximenes
authors.affiliation: Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo, 5.790, Bloco I-90, Maringá, PR, 87020-900, Brazil. lautenschlager@uem.br.
authors.forename: Sueli
authors.initials: S
authors.lastname: de Oliveira Silva
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D024483:Vitamin K 3 / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D024483:Vitamin K 3
keywords: Apoptosis SiHa cells; Human Papillomavirus; Vitamin K3