In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico

Author:

Ramírez-Santos Jesica12ORCID,Calzada Fernando2ORCID,Ordoñez-Razo Rosa María3ORCID,Mendieta-Wejebe Jessica Elena1ORCID,Velázquez-Domínguez José Antonio4ORCID,Argüello-García Raúl5,Velázquez Claudia6,Barbosa Elizabeth1ORCID

Affiliation:

1. Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Plan de San Luis y Salvador Díaz Mirón S/N, Col. Casco de Santo Tomás, Mexico City 11340, Mexico

2. Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades 2° Piso CORSE Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06720, Mexico

3. Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría, 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, Mexico

4. Instituto Politécnico Nacional, Escuela Nacional de Medicina y Homeopatía, Av. Guillermo Massieu Helguera 239, La Purísima Ticoman, Gustavo A. Madero, Mexico City 07320, Mexico

5. Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City 07360, Mexico

6. 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 42076, Mexico

Abstract

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin’s lymphoma.

Publisher

MDPI AG

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