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Vitamin K3 induces antiproliferative effect in cervical epithelial cells transformed by HPV 16 (SiHa cells) through the increase in reactive oxygen species production

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

Our data showed that vitamin K3 generates an oxidative imbalance in SiHa cells, leading to mechanisms that induce cell death by apoptosis.

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Abbreviations

ANOVA:

One-way analysis of variance

CCCP:

Carbonyl cyanide 3- clorophenylhydrazone

DHR:

Dihydrorhodamine 123

DIC:

Differential interference contrast microscopy

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethylsulfoxide

EDTA:

Ethylenediaminetetraacetic acid

FACS:

Calibur flow cytometer

FSC-H:

Forward light scatter

H2DCF-DA:

2′,7′-dichlorodihydrofluorescein diacetate

HPV 16:

SiHa cells

HPV:

Human papillomavirus

IC50:

50 % inhibitory concentration

IC90:

90 % inhibitory concentration

IV:

Index of variation

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

OD:

Optical density

PI:

Propidium idodite

PSN:

Penicillin–streptomycin–neomycin antibiotic

RFU:

Relative fluorescence units

Rh123:

Rhodamine123

ROS:

Reactive oxygen species

VERO:

Cercopithecus aethiops

ΔΨm:

Mitochondrial membrane potential assay

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Acknowledgments

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) e Fundação Araucária.

Author information

Authors and Affiliations

  1. Programa de Pós-graduação em Biociências Aplicadas á Farmácia, Universidade Estadual de Maringá, Av. Colombo, 5.790, 87020-900, Maringá, PR, Brazil

    Natália de Carvalho Scharf Santana, Natália Alves Lima & Bianca Altrão Ratti

  2. Programa de Pós-graduação em Ciências da Saúde, Universidade Estadual de Maringá, Av Colombo, 5.790, Maringá, PR, 87020-900, Brazil

    Patrícia de Souza Bonfim Mendonça

  3. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av Colombo, 5.790, Maringá, PR, 87020-900, Brazil

    Vânia Cristina Desoti & Danielle Lazarin Bidóia

  4. Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo, 5.790, Bloco I-90, Maringá, PR, 87020-900, Brazil

    Tânia Ueda Nakamura, Celso Vataru Nakamura & Sueli de Oliveira Silva

  5. Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Av. Colombo, 5.790, Maringá, PR, 87020-900, Brazil

    Marcia Edilaine Lopes Consolaro

  6. 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

    Valdecir Farias Ximenes

Authors
  1. Natália de Carvalho Scharf Santana
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  2. Natália Alves Lima
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  3. Vânia Cristina Desoti
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  6. Bianca Altrão Ratti
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  7. Tânia Ueda Nakamura
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  8. Celso Vataru Nakamura
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  9. Marcia Edilaine Lopes Consolaro
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  10. Valdecir Farias Ximenes
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  11. Sueli de Oliveira Silva
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Corresponding author

Correspondence to Sueli de Oliveira Silva.

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Ethical standards

This study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes), Financiadora de Estudos e Projetos, Fundação Araucária. Programa de Pós Graduação em Biociências e Fisiopatologia da Universidade Estadual de Maringá, and Complexo de Centrais de Apoio a Pesquisa–UEM.

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All authors have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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de Carvalho Scharf Santana, N., Lima, N.A., Desoti, V.C. et al. Vitamin K3 induces antiproliferative effect in cervical epithelial cells transformed by HPV 16 (SiHa cells) through the increase in reactive oxygen species production. Arch Gynecol Obstet 294, 797–804 (2016). https://doi.org/10.1007/s00404-016-4097-7

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