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


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Title:
Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment
Authors:
Ruiz Torres, Verónica
Rodríguez Pérez, Celia
Herranz López, María Dolores
Martín García, Beatriz
Gómez Caravaca, Ana María
Arráez Román, David
Segura Carretero, Antonio
Barrajón Catalán, Enrique
Micol Molina, Vicente
Department:
Departamentos de la UMH::Ingeniería
Issue Date:
2019-11-23
Abstract:
Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative e_ects 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 e_ects 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
Keywords/Subjects:
marine invertebrate
soft coral
holothurian
nudibranch
antiproliferative
colon cancer
ROS
DNA damage
cell cycle
apoptosis
necrosis
HPLC-ESI-TOF-MS
cell death
natural compounds
Type of document:
application/pdf
Access rights:
info:eu-repo/semantics/openAccess
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