Antilymphoma Effect of Incomptine A: In Vivo, In Silico, and Toxicological Studies
Fernando Calzada,
Elihú Bautista,
Sergio Hidalgo-Figueroa,
Normand García-Hernández,
Elizabeth Barbosa,
Claudia Velázquez,
Rosa María Ordoñez-Razo,
Angel Giovanni Arietta-García
Affiliations
Fernando Calzada
Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico
Elihú Bautista
CONACYT—Consorcio de Investigación, Innovación y Desarrollo para las Zonas Áridas, Instituto Potosino de Investigación Científica y Tecnológica A. C., San Luis Potosí CP 78216, Mexico
Sergio Hidalgo-Figueroa
CONACYT—Consorcio de Investigación, Innovación y Desarrollo para las Zonas Áridas, Instituto Potosino de Investigación Científica y Tecnológica A. C., San Luis Potosí CP 78216, Mexico
Normand García-Hernández
Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría, 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico
Elizabeth Barbosa
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City CP 11340, Mexico
Claudia Velázquez
Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Km 4.5, Carretera Pachuca-Tulancingo, Unidad Universitaria, Pachuca CP 42076, Mexico
Rosa María Ordoñez-Razo
Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría, 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico
Angel Giovanni Arietta-García
Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría, 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico
Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.
