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. 2022 Feb;395(2):267-274.
doi: 10.1007/s00210-021-02185-0. Epub 2021 Dec 2.

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

Renata A de Abrantes  1 , Tatianne M Batista  1 , Vivianne M Mangueira  1 , Tatyanna K G de Sousa  1 , Rafael C Ferreira  1 , Ana Paula G Moura  1 , Lucas S Abreu  1 , Adriano F Alves  2 , Eudes S Velozo  3 , Leônia M Batista  1   4 , Marcelo S da Silva  1   4 , Josean F Tavares  1   4 , Marianna V Sobral  5   6
Affiliations

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

Renata A de Abrantes et al. Naunyn Schmiedebergs Arch Pharmacol. 2022 Feb.

Abstract

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 LD50 (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.

Keywords: Angiogenesis; Ehrlich tumor; Tonantzitlolone B; Toxicity.

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