In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B

Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-t...

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Autores principales:	Silva, I.T., Carvalho, A., Lang, K.L., Dudek, S.E., Masemann, D., Durán, F.J., Caro, M.S.B., Rapp, U.R., Wixler, V., Schenkel, E.P., Simões, C.M.O., Ludwig, S.
Formato:	JOUR
Materias:	2 deoxy 2 amine cucurbitacin E caspase 3 cucurbitacin epidermal growth factor receptor mitogen activated protein kinase protein kinase B Raf protein STAT3 protein staurosporine surfactant protein C unclassified drug antineoplastic agent apoptosis regulatory protein cucurbitacin B phosphatidylinositol 3 kinase triterpene animal cell animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cell cycle arrest cell proliferation controlled study drug structure G2 phase cell cycle checkpoint human human cell in vitro study in vivo study lung alveolus epithelium male non small cell lung cancer nonhuman protein expression protein phosphorylation signal transduction animal Carcinoma, Non-Small-Cell Lung cell cycle checkpoint cytoskeleton disease model drug effects drug screening genetics Lung Neoplasms metabolism mouse pathology phosphorylation synthesis transgenic mouse tumor cell line Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Caspase 3 Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation Cytoskeleton Disease Models, Animal Humans Male Mice Mice, Transgenic Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt raf Kinases Receptor, Epidermal Growth Factor Signal Transduction STAT3 Transcription Factor Triterpenes Tumor Stem Cell Assay Xenograft Model Antitumor Assays
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Silva
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_19326203_v10_n2_p_Silva2023-10-03T16:34:35Z In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B Silva, I.T. Carvalho, A. Lang, K.L. Dudek, S.E. Masemann, D. Durán, F.J. Caro, M.S.B. Rapp, U.R. Wixler, V. Schenkel, E.P. Simões, C.M.O. Ludwig, S. 2 deoxy 2 amine cucurbitacin E caspase 3 cucurbitacin epidermal growth factor receptor mitogen activated protein kinase protein kinase B Raf protein STAT3 protein staurosporine surfactant protein C unclassified drug antineoplastic agent apoptosis regulatory protein caspase 3 cucurbitacin B epidermal growth factor receptor phosphatidylinositol 3 kinase protein kinase B Raf protein STAT3 protein triterpene animal cell animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cell cycle arrest cell proliferation controlled study drug structure G2 phase cell cycle checkpoint human human cell in vitro study in vivo study lung alveolus epithelium male non small cell lung cancer nonhuman protein expression protein phosphorylation signal transduction animal Carcinoma, Non-Small-Cell Lung cell cycle checkpoint cytoskeleton disease model drug effects drug screening genetics Lung Neoplasms metabolism mouse pathology phosphorylation synthesis transgenic mouse tumor cell line Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Carcinoma, Non-Small-Cell Lung Caspase 3 Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation Cytoskeleton Disease Models, Animal Humans Lung Neoplasms Male Mice Mice, Transgenic Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt raf Kinases Receptor, Epidermal Growth Factor Signal Transduction STAT3 Transcription Factor Triterpenes Tumor Stem Cell Assay Xenograft Model Antitumor Assays Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug. © 2015 Silva et al. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Silva
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	2 deoxy 2 amine cucurbitacin E caspase 3 cucurbitacin epidermal growth factor receptor mitogen activated protein kinase protein kinase B Raf protein STAT3 protein staurosporine surfactant protein C unclassified drug antineoplastic agent apoptosis regulatory protein caspase 3 cucurbitacin B epidermal growth factor receptor phosphatidylinositol 3 kinase protein kinase B Raf protein STAT3 protein triterpene animal cell animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cell cycle arrest cell proliferation controlled study drug structure G2 phase cell cycle checkpoint human human cell in vitro study in vivo study lung alveolus epithelium male non small cell lung cancer nonhuman protein expression protein phosphorylation signal transduction animal Carcinoma, Non-Small-Cell Lung cell cycle checkpoint cytoskeleton disease model drug effects drug screening genetics Lung Neoplasms metabolism mouse pathology phosphorylation synthesis transgenic mouse tumor cell line Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Carcinoma, Non-Small-Cell Lung Caspase 3 Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation Cytoskeleton Disease Models, Animal Humans Lung Neoplasms Male Mice Mice, Transgenic Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt raf Kinases Receptor, Epidermal Growth Factor Signal Transduction STAT3 Transcription Factor Triterpenes Tumor Stem Cell Assay Xenograft Model Antitumor Assays
spellingShingle	2 deoxy 2 amine cucurbitacin E caspase 3 cucurbitacin epidermal growth factor receptor mitogen activated protein kinase protein kinase B Raf protein STAT3 protein staurosporine surfactant protein C unclassified drug antineoplastic agent apoptosis regulatory protein caspase 3 cucurbitacin B epidermal growth factor receptor phosphatidylinositol 3 kinase protein kinase B Raf protein STAT3 protein triterpene animal cell animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cell cycle arrest cell proliferation controlled study drug structure G2 phase cell cycle checkpoint human human cell in vitro study in vivo study lung alveolus epithelium male non small cell lung cancer nonhuman protein expression protein phosphorylation signal transduction animal Carcinoma, Non-Small-Cell Lung cell cycle checkpoint cytoskeleton disease model drug effects drug screening genetics Lung Neoplasms metabolism mouse pathology phosphorylation synthesis transgenic mouse tumor cell line Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Carcinoma, Non-Small-Cell Lung Caspase 3 Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation Cytoskeleton Disease Models, Animal Humans Lung Neoplasms Male Mice Mice, Transgenic Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt raf Kinases Receptor, Epidermal Growth Factor Signal Transduction STAT3 Transcription Factor Triterpenes Tumor Stem Cell Assay Xenograft Model Antitumor Assays Silva, I.T. Carvalho, A. Lang, K.L. Dudek, S.E. Masemann, D. Durán, F.J. Caro, M.S.B. Rapp, U.R. Wixler, V. Schenkel, E.P. Simões, C.M.O. Ludwig, S. In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
topic_facet	2 deoxy 2 amine cucurbitacin E caspase 3 cucurbitacin epidermal growth factor receptor mitogen activated protein kinase protein kinase B Raf protein STAT3 protein staurosporine surfactant protein C unclassified drug antineoplastic agent apoptosis regulatory protein caspase 3 cucurbitacin B epidermal growth factor receptor phosphatidylinositol 3 kinase protein kinase B Raf protein STAT3 protein triterpene animal cell animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cell cycle arrest cell proliferation controlled study drug structure G2 phase cell cycle checkpoint human human cell in vitro study in vivo study lung alveolus epithelium male non small cell lung cancer nonhuman protein expression protein phosphorylation signal transduction animal Carcinoma, Non-Small-Cell Lung cell cycle checkpoint cytoskeleton disease model drug effects drug screening genetics Lung Neoplasms metabolism mouse pathology phosphorylation synthesis transgenic mouse tumor cell line Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Carcinoma, Non-Small-Cell Lung Caspase 3 Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation Cytoskeleton Disease Models, Animal Humans Lung Neoplasms Male Mice Mice, Transgenic Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt raf Kinases Receptor, Epidermal Growth Factor Signal Transduction STAT3 Transcription Factor Triterpenes Tumor Stem Cell Assay Xenograft Model Antitumor Assays
description	Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug. © 2015 Silva et al.
format	JOUR
author	Silva, I.T. Carvalho, A. Lang, K.L. Dudek, S.E. Masemann, D. Durán, F.J. Caro, M.S.B. Rapp, U.R. Wixler, V. Schenkel, E.P. Simões, C.M.O. Ludwig, S.
author_facet	Silva, I.T. Carvalho, A. Lang, K.L. Dudek, S.E. Masemann, D. Durán, F.J. Caro, M.S.B. Rapp, U.R. Wixler, V. Schenkel, E.P. Simões, C.M.O. Ludwig, S.
author_sort	Silva, I.T.
title	In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
title_short	In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
title_full	In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
title_fullStr	In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
title_full_unstemmed	In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
title_sort	in vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin b
url	http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Silva
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In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B

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