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

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

Naunyn-Schmiedeberg's archives of pharmacology, 2022-02, Vol.395 (2), p.267-274 [Periódico revisado por pares]

Berlin/Heidelberg: Springer Berlin Heidelberg

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Título:
Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea
Autor: de Abrantes, Renata A. ; Batista, Tatianne M. ; Mangueira, Vivianne M. ; de Sousa, Tatyanna K. G. ; Ferreira, Rafael C. ; Moura, Ana Paula G. ; Abreu, Lucas S. ; Alves, Adriano F. ; Velozo, Eudes S. ; Batista, Leônia M. ; da Silva, Marcelo S. ; Tavares, Josean F. ; Sobral, Marianna V.
Assuntos: Angiogenesis ; Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - pharmacology ; Angiogenesis Inhibitors - toxicity ; Animals ; Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - pharmacology ; Antineoplastic Agents, Phytogenic - toxicity ; Antitumor activity ; Antitumor agents ; Antiviral agents ; Ascites ; Biomedical and Life Sciences ; Biomedicine ; Brief Communication ; Cancer ; Carcinoma, Ehrlich Tumor - drug therapy ; Cell Line, Tumor ; Cytotoxicity ; Diterpenes ; Diterpenes - administration & dosage ; Diterpenes - pharmacology ; Diterpenes - toxicity ; Dose-Response Relationship, Drug ; Drug discovery ; Euphorbiaceae - chemistry ; Female ; Genotoxicity ; Kidneys ; Lethal dose ; Lethal Dose 50 ; Macrocyclic Compounds - administration & dosage ; Macrocyclic Compounds - pharmacology ; Macrocyclic Compounds - toxicity ; Mice ; Micronucleus Tests ; Natural products ; Neurosciences ; Nitric oxide ; Nitric Oxide - metabolism ; Pharmacology/Toxicology ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Tumors
É parte de: Naunyn-Schmiedeberg's archives of pharmacology, 2022-02, Vol.395 (2), p.267-274
Descrição: 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.
Editor: Berlin/Heidelberg: Springer Berlin Heidelberg
Idioma: Inglês

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

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

Berlin/Heidelberg: Springer Berlin Heidelberg

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