A Higher Frequency Administration of the Nontoxic Cycloartane-Type Triterpene Argentatin A Improved Its Anti-Tumor Activity

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-04, Vol.25 (8), p.1780
• Main Authors: Tavarez-Santamaría, Zaira, Jacobo-Herrera, Nadia J, Rocha-Zavaleta, Leticia, Zentella-Dehesa, Alejandro, Couder-García, Beatriz Del Carmen, Martínez-Vázquez, Mariano
• Format: Article
• Language: English
• Subjects: Animals; Annexin V; Antineoplastic Agents - administration & dosage; antiproliferative; Antitumor activity; Apoptosis; Apoptosis - drug effects; Argentatin A; beta-Galactosidase - metabolism; Biocompatibility; Biomarkers; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; cell senescence; Cisplatin; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Cytotoxicity; Disease Models, Animal; Drug Evaluation, Preclinical; Evaluation; Galactosidase; Guayule; Humans; Immunohistochemistry; In vivo methods and tests; Industrial wastes; Iodides; Metabolites; Mice; Molecular Structure; Natural rubber; Parthenium argentatum; Polyimide resins; Proliferating cell nuclear antigen; Propidium iodide; Rubber; Senescence; Toxicity; Triterpenes - administration & dosage; Tumor Burden - drug effects; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; β-Galactosidase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25081780

(Gray), commonly known as guayule, has been used to obtain natural rubber since the beginning of the 20th century. Additionally, the so called "resin" is a waste product derived from the industrial process. The cycloartane-type triterpene Argentatin A (AA) is one of the main constituents of the industrial waste resin. In this study we evaluated the AA anticancer activity both in vitro and in vivo in the HCT116 colon cancer cells. The apoptosis promotion of AA was assessed by the annexin V/propidium iodide (PI) assay. The senescence was evaluated for SA-β-galactosidase, and PCNA was used as a marker of proliferation. Its antitumor activity was evaluated using a xenograft mouse model. The results indicated that AA-induced apoptosis in HCT-116 cells and was positively stained for SA-β-galactosidase. In the xenografted mice test, the administration of AA at the dose of 250 mg/kg three times a week for 21 days reduced tumor growth by 78.1%. A comparable tumor reduction was achieved with cisplatin at the dose of 2 mg/kg administered three times a week for 21 days. However, nude mice treated with AA did not lose weight, as they did remarkably when treated with cisplatin. Furthermore, the animals treated with AA showed similar blood profiles as the healthy control group. These data indicate the low toxicity of AA compared to that shown by cisplatin.