Antiproliferative activity and chemical composition of the venom from the Amazonian toad Rhinella marina (Anura: Bufonidae).
Little is known on the composition of Peruvian Amazon toad venoms. The large toad Rhinella marina is common in the cleared tropical forests of the Iquitos region and is regarded as poisonous. The venom from two different populations of R. marina was collected in the Departamento de Loreto, Perú. The samples were assessed for antiproliferative effect and composition. Some 29 compounds were identified or tentatively identified from the venom by spectroscopic and spectrometric means. The main free bufadienolide was marinobufagin 7 while marinobufotoxin 15 and bufalitoxin 9 were the main bufadienolide argininyl diacid derivatives. The alkaloids dehydrobufotenin 28 and bufotenidin 29 were present in both venoms. The main difference in the venoms was the relative ratio of argininyl diacids from bufadienolides to free bufadienolides. The argininyl diacids included derivatives from bufalin, marinobufagin, telocinobufagin, hellebrigenin, resibufogenin and bufotalinin. Four compounds, including undecadienoyl aginine 6 and three argininyl diacids from bufadienolides were tentatively identified for the first time in the samples. The venom showed a strong antiproliferative effect towards MRC-5 normal human lung fibroblasts (0.063-0.247 μg/mL), AGS human gastric adenocarcinoma cells (0.076-0.272 μg/mL), SK-MES-1 human lung cancer cells (0.154-0.296 μg/mL), J82 human bladder carcinoma cells (0.169-0.212 μg/mL), and HL-60 human promyelocytic leukemia (0.071-0.283 μg/mL). The antiproliferative effect is mediated by ROS production and cell cycle arrest in human breast cancer cells (MCF7 and MDA-MB-231). This is the first report on the composition of R. marina venom from the Peruvian Amazon pointing out the need to include different venom samples to get a better picture from the activity and composition of South American toad defense substances.
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile. Electronic address: schmeda@utalca.cl.
Guillermo
G
Schmeda-Hirschmann
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile; Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique, Chile.
Cristina
C
Quispe
Universidad Científica del Perú, Av. Abelardo Quiñones Km 2.5, Iquitos, Peru.
Gabriel Vargas
GV
Arana
Laboratorio de Cultivo Celular, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, 3460000 Talca, Chile.
Cristina
C
Theoduloz
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile and Geroscience Center for Brain Health and Metabolism, Independencia 1027, Casilla 7, Santiago, Chile.
Félix A
FA
Urra
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile and Geroscience Center for Brain Health and Metabolism, Independencia 1027, Casilla 7, Santiago, Chile.
César
C
Cárdenas
D000664:Amphibian Venoms / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002025:Bufonidae; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D053719:Tandem Mass Spectrometry
D000664:Amphibian Venoms
Antiproliferative activity; Argininyl bufadienolides; Bufo; Peruvian Amazon; Rhinella marina