title: Mitochondria and redox homoeostasis as chemotherapeutic targets of Araucaria angustifolia (Bert.) O. Kuntze in human larynx HEp-2 cancer cells.
abstract: Natural products are among one of the most promising fields in finding new molecular targets in cancer therapy. Laryngeal carcinoma is one of the most common cancers affecting the head and neck regions, and is associated with high morbidity rate if left untreated. The aim of this study was to examine the antiproliferative effect of Araucaria angustifolia on laryngeal carcinoma HEp-2 cells. The results showed that A. angustifolia extract (AAE) induced a significant cytotoxicity in HEp-2 cells compared to the non-tumor human epithelial (HEK-293) cells, indicating a selective activity of AAE for the cancer cells. A. angustifolia extract was able to increase oxidative damage to lipids and proteins, and the production of nitric oxide, along with the depletion of enzymatic antioxidant defenses (superoxide dismutase and catalase) in the tumor cell line. Moreover, AAE was able to induce DNA damage, nuclear fragmentation and chromatin condensation. A significant increase in the Apoptosis Inducing Factor (AIF), Bax, poly-(ADP-ribose) polymerase (PARP) and caspase-3 cleavage expression were also found. These effects could be related to the ability of AAE to increase the production of reactive oxygen species through inhibition of the mitochondrial electron transport chain complex I activity and ATP production by the tumor cells. The phytochemical analysis of A. angustifolia, performed using High Resolution Mass Spectrometry (HRMS) in MS and MS/MS mode, showed the presence of dodecanoic and hexadecanoic acids, and phenolic compounds, which may be associated with the chemotherapeutic effect observed in this study.
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Cátia dos Santos
authors.initials: Cdos S
authors.lastname: Branco
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Émilin Dreher
authors.initials: ÉD
authors.lastname: de Lima
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Tiago Selau
authors.initials: TS
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Thamiris Becker
authors.initials: TB
authors.lastname: Scheffel
authors.affiliation: University of Toronto, Medical Science Building, Room 4204, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Claudia Cilene Fernandes Correia
authors.initials: CC
authors.lastname: Laurino
authors.affiliation: Laboratório de Biotecnologia de Produtos Naturais e Sintéticos, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil.
authors.forename: Sidnei
authors.initials: S
authors.lastname: Moura
authors.affiliation: Laboratório de Estresse Oxidativo e Antioxidantes, Instituto de Biotecnologia, Universidade de Caxias do Sul, RS 95070560, Brazil. Electronic address: msalvado@ucs.br.
authors.forename: Mirian
authors.initials: M
authors.lastname: Salvador
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007830:Larynx / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D064028:Tracheophyta / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Apoptosis; Araucaria angustifolia; HEp-2; HRMS; Mitochondria