Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment
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AuthorRuiz Torres, Verónica; Rodríguez-Pérez, Celia; Herranz-López, María; Martín-García, Beatriz; Gómez-Caravaca, Ana María; Arráez Román, David; Segura Carretero, Antonio; Barrajón-Catalán, Enrique; Micol Molina, Vicente
Marine invertebratesSoft coralColon cancerDNA damageCell cycleCell deathNatural compounds
Ruiz-Torres, V., Rodríguez-Pérez, C., Herranz-López, M., Martín-García, B., Gómez-Caravaca, A. M., Arráez-Román, D., ... & Micol, V. (2019). Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment. Biomolecules, 9(12), 771.
SponsorshipThis research was funded by projects AGL2015-67995-C3-1-R, AGL2015-67995-C3-2-R AGL2015-67995-C3-3-R, RTI2018-096724-B-C21, and 2018-096724-B-C22 from the Spanish Ministry of Science, Innovation and Universities; Project P11-CTS-7625 from Andalusian Regional Government Council of Innovation and Science; projects PROMETEO/2012/007, PROMETEO/2016/006, and VALi+D fellowship (ACIF/2015/158) from Generalitat Valenciana to VR-Tand CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn).
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/Mtransition, 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.