Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea.

Autor: de Abrantes RA; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Batista TM; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Mangueira VM; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., de Sousa TKG; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Ferreira RC; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Moura APG; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Abreu LS; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Alves AF; Department of Physiology and Pathology, Federal University of Paraíba, João Pessoa, PB, Brazil., Velozo ES; Research Laboratory in Materia Medica, School of Pharmacy, Federal University of Bahia, Salvador, Brazil., Batista LM; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil., da Silva MS; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil., Tavares JF; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil., Sobral MV; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil. mariannavbs@gmail.com.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil. mariannavbs@gmail.com.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2022 Feb; Vol. 395 (2), pp. 267-274. Date of Electronic Publication: 2021 Dec 02.
DOI: 10.1007/s00210-021-02185-0
Abstrakt: Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally - i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD 50 (lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor's volume and total viable cancer cell count (p < 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (p < 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (p < 0.05) and nitric oxide (p < 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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