Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/28894
Title: β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells
Authors: Dias, Rosane Borges
Araújo, Taís Bacelar Sacramento de
Freitas, Raíza Dias de
Rodrigues, Ana Carolina Borges da Cruz
Sousa, Letícia Palmeira
Sales, Caroline Brandi Schlaepfer
Valverde, Ludmila de Faro
Soares, Milena Botelho Pereira
Reis, Mitermayer Galvão dos
Coletta, Ricardo Della
Ramos, Eduardo Antônio Gonçalves
Camara, Celso Amorim
Silva, Tania Maria Sarmento
Barbosa Filho, José Maria
Bezerra, Daniel Pereira
Rocha, Clarissa Araújo Gurgel
Affilliation: Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Bahia. Institute of Health Sciences. Department of Biomorphology. Salvador, BA, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pathology and Forensic Medicine. Salvador, BA, Brazil
University of Campinas. School of Dentistry. Department of Oral Diagnosis. Piracicaba, SP, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pathology and Forensic Medicine. Salvador, BA, Brazil
Federal Rural University of Pernambuco. Department of Chemistry. Recife, PE, Brazil
Federal Rural University of Pernambuco. Department of Chemistry. Recife, PE, Brazil
Federal University of Paraiba. Pharmaceutical Technology Laboratory. João Pessoa, PB, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Laboratory of Oral Surgical Pathology, School of Dentistry. Salvador, BA, Brazil
Abstract: β-Lapachone is a natural naphthoquinone originally obtained from the bark of the purple Ipe (Tabebuia avellanedae Lor, Bignoniaceae) and its therapeutic potential in human cancer cells has been evaluated in several studies. In this study, we examined the effects of β-lapachone and its 3-iodine derivatives (3-I-α-lapachone and 3-I-β-lapachone) on cell proliferation, cell death, and cancer-related gene expression in human oral squamous cell carcinoma cells. β-Lapachone and its 3-iodine derivatives showed potent cytotoxicity against different types of human cancer cell lines. Indeed, treatment with these compounds induced cell cycle arrest at G2/M phase, followed by internucleosomal DNA fragmentation, and caused significant increases in phosphatidylserine externalization, caspase-8 and -9 activation, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, and apoptotic cell death morphology. The apoptosis induced by the compounds was prevented by pretreatment with a pan-caspase inhibitor (Z-VAD-FMK) and an antioxidant (N-acetyl-l-cysteine). In vivo, β-lapachone and its 3-iodine derivatives significantly reduced tumor burden and did not alter any of the biochemical, hematological, or histological parameters of the animals. Overall, β-lapachone and its 3-iodine derivatives showed promising cytotoxic activity due to their ability to induce cell cycle arrest at G2/M phase and promote caspase- and ROS-mediated apoptosis. In addition, β-lapachone and its 3-iodine derivatives were able to suppress tumor growth in vivo, indicating that these compounds may be new antitumor drug candidates.
Keywords: β-Lapachone
Oral cancer
Chemotherapy
Natural products
keywords: β-Lapachona
Câncer bucal
Quimioterapia
Produtos naturais
Issue Date: 2018
Publisher: Elsevier
Citation: DIAS, R. B. et al. β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells. Free Radical Biology and Medicine, v. 126, p. 87–100, 2018.
DOI: 10.1016/j.freeradbiomed.2018.07.022
ISSN: 0891-5849
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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