Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model
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 stud...
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todo:paper_0041008X_v329_n_p272_Marostica2023-10-03T14:51:16Z Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model 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 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 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 JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0041008X_v329_n_p272_Marostica |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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 |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Marostica, L.L. |
| title |
Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model |
| title_short |
Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model |
| title_full |
Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model |
| title_fullStr |
Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model |
| title_full_unstemmed |
Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model |
| title_sort |
antitumor effectiveness of a combined therapy with a new cucurbitacin b derivative and paclitaxel on a human lung cancer xenograft model |
| url |
http://hdl.handle.net/20.500.12110/paper_0041008X_v329_n_p272_Marostica |
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