Artículo

Marostica, L.L.; de Barros, A.L.B.; Oliveira, J.; Salgado, B.S.; Cassali, G.D.; Leite, E.A.; Cardoso, V.N.; Lang, K.L.; Caro, M.S.B.; Durán, F.J.; Schenkel, E.P.; de Oliveira, M.C.; Simões, C.M.O. "Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model" (2017) Toxicology and Applied Pharmacology. 329:272-281
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Abstract:

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells. In sequence, the purpose of this study was to evaluate the in vivo antitumor efficacy of this combined therapy as well as with these drugs individually, using a human NSCLC xenograft model. Some indicators of sub chronic toxicity that could be affected by treatments were also assessed. The results obtained in vivo with the combined treatment (1 mg/kg + PTX 10 mg/kg) showed the most effective reduction of the relative tumor volume and the highest inhibition of tumor growth and proliferation, when compared with those of the single treatments. Furthermore, scintigraphic images, obtained before and after the treatments, showed that the most effective protocol able to reduce the residual viable tumor mass was the combined treatment. All treatment regimens were well tolerated without significant changes in body weight and no histological and functional damage to liver and kidney tissues. These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC. © 2017

Registro:

Documento: Artículo
Título:Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model
Autor:Marostica, L.L.; de Barros, A.L.B.; Oliveira, J.; Salgado, B.S.; Cassali, G.D.; Leite, E.A.; Cardoso, V.N.; Lang, K.L.; Caro, M.S.B.; Durán, F.J.; Schenkel, E.P.; de Oliveira, M.C.; Simões, C.M.O.
Filiación:Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, Santa Catarina CEP 88040-900, Brazil
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil
Departamento de Patologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Campus Maruípe, Vitória, Espírito Santo CEP 29075-910, Brazil
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil
Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC CEP 88040-900, Brazil
UMYMFOR-CONICET, Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Antitumor effect; Cucurbitacins; Lung cancer; Paclitaxel; Scintigraphic images; Xenograft lung tumor; 2 deoxy 2 amine cucurbitacin E; cucurbitacin; paclitaxel; unclassified drug; antineoplastic agent; cucurbitacin B; Ki 67 antigen; paclitaxel; radiopharmaceutical agent; triterpene; animal experiment; animal model; antineoplastic activity; antiproliferative activity; cancer inhibition; cancer size; chronic toxicity; combination chemotherapy; controlled study; drug efficacy; drug potentiation; drug screening; drug tolerability; female; human; human cell; immunohistochemistry; in vivo study; mouse; non small cell lung cancer; nonhuman; Review; scintigraphy; tumor xenograft; A-549 cell line; animal; Bagg albino mouse; Carcinoma, Non-Small-Cell Lung; cell proliferation; diagnostic imaging; drug effects; Lung Neoplasms; metabolism; nude mouse; pathology; time factor; toxicity testing; tumor volume; whole body imaging; A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Female; Humans; Ki-67 Antigen; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Paclitaxel; Radiopharmaceuticals; Time Factors; Toxicity Tests, Subchronic; Triterpenes; Tumor Burden; Whole Body Imaging; Xenograft Model Antitumor Assays
Año:2017
Volumen:329
Página de inicio:272
Página de fin:281
DOI: http://dx.doi.org/10.1016/j.taap.2017.06.007
Título revista:Toxicology and Applied Pharmacology
Título revista abreviado:Toxicol. Appl. Pharmacol.
ISSN:0041008X
CODEN:TXAPA
CAS:paclitaxel, 33069-62-4; cucurbitacin B; Ki-67 Antigen; Paclitaxel; Radiopharmaceuticals; Triterpenes
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0041008X_v329_n_p272_Marostica

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Citas:

---------- APA ----------
Marostica, L.L., de Barros, A.L.B., Oliveira, J., Salgado, B.S., Cassali, G.D., Leite, E.A., Cardoso, V.N.,..., Simões, C.M.O. (2017) . Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model. Toxicology and Applied Pharmacology, 329, 272-281.
http://dx.doi.org/10.1016/j.taap.2017.06.007
---------- CHICAGO ----------
Marostica, L.L., de Barros, A.L.B., Oliveira, J., Salgado, B.S., Cassali, G.D., Leite, E.A., et al. "Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model" . Toxicology and Applied Pharmacology 329 (2017) : 272-281.
http://dx.doi.org/10.1016/j.taap.2017.06.007
---------- MLA ----------
Marostica, L.L., de Barros, A.L.B., Oliveira, J., Salgado, B.S., Cassali, G.D., Leite, E.A., et al. "Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model" . Toxicology and Applied Pharmacology, vol. 329, 2017, pp. 272-281.
http://dx.doi.org/10.1016/j.taap.2017.06.007
---------- VANCOUVER ----------
Marostica, L.L., de Barros, A.L.B., Oliveira, J., Salgado, B.S., Cassali, G.D., Leite, E.A., et al. Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model. Toxicol. Appl. Pharmacol. 2017;329:272-281.
http://dx.doi.org/10.1016/j.taap.2017.06.007