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Open AccessArticle

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

1
Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández (UMH), 03202 Elche, Spain
2
Department of Analytical Chemistry, Faculty of Sciences, University of Granada, 18071 Granada, Spain
3
Research and Development of Functional Food Centre (CIDAF), PTS Granada, Edificio BioRegion, 18016 Granada, Spain
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CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III., Palma de Mallorca 07122, Spain
*
Author to whom correspondence should be addressed.
Both authors share senior co-authorship.
Biomolecules 2019, 9(12), 771; https://doi.org/10.3390/biom9120771
Received: 2 September 2019 / Revised: 23 October 2019 / Accepted: 29 October 2019 / Published: 23 November 2019
(This article belongs to the Special Issue Mechanisms of Cell Death in Disease: A New Therapeutic Opportunity)
Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative effects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative effects and induced cell cycle arrest at the G2/M transition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis. View Full-Text
Keywords: marine invertebrate; soft coral; holothurian; nudibranch; antiproliferative; colon cancer; ROS; DNA damage; cell cycle; apoptosis; necrosis; HPLC-ESI-TOF-MS; cell death; natural compounds marine invertebrate; soft coral; holothurian; nudibranch; antiproliferative; colon cancer; ROS; DNA damage; cell cycle; apoptosis; necrosis; HPLC-ESI-TOF-MS; cell death; natural compounds
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Ruiz-Torres, V.; Rodríguez-Pérez, C.; Herranz-López, M.; Martín-García, B.; Gómez-Caravaca, A.-M.; Arráez-Román, D.; Segura-Carretero, A.; Barrajón-Catalán, E.; Micol, V. Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment. Biomolecules 2019, 9, 771.

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