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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" (2015) PLoS ONE. 10(2)
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Abstract:

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.

Registro:

Documento: Artículo
Título:In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
Autor: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.
Filiación:Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
Institute of Molecular Virology (IMV), Center of Molecular Biology of Inflammation (ZMBE), Westfaelische-Wilhelms-University, Muenster, Germany
UMYMFOR, Department of Organic Chemistry, Universidad de Buenos Aires, Buenos Aires, Argentina
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
Cells in Motion, Cluster of Excellence, Westfaelische-Wilhelms-University, Muenster, Germany
Interdisciplinary Center of Clinical Research (IZKF), Westfaelische-Wilhelms-University, Muenster, Germany
Palabras clave: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
Año:2015
Volumen:10
Número:2
DOI: http://dx.doi.org/10.1371/journal.pone.0117794
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:caspase 3, 169592-56-7; epidermal growth factor receptor, 79079-06-4; mitogen activated protein kinase, 142243-02-5; protein kinase B, 148640-14-6; staurosporine, 62996-74-1; phosphatidylinositol 3 kinase, 115926-52-8; Antineoplastic Agents; Apoptosis Regulatory Proteins; Caspase 3; cucurbitacin B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; raf Kinases; Receptor, Epidermal Growth Factor; STAT3 Transcription Factor; Triterpenes
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n2_p_Silva

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Citas:

---------- APA ----------
Silva, I.T., Carvalho, A., Lang, K.L., Dudek, S.E., Masemann, D., Durán, F.J., Caro, M.S.B.,..., Ludwig, S. (2015) . In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B. PLoS ONE, 10(2).
http://dx.doi.org/10.1371/journal.pone.0117794
---------- CHICAGO ----------
Silva, I.T., Carvalho, A., Lang, K.L., Dudek, S.E., Masemann, D., Durán, F.J., et al. "In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B" . PLoS ONE 10, no. 2 (2015).
http://dx.doi.org/10.1371/journal.pone.0117794
---------- MLA ----------
Silva, I.T., Carvalho, A., Lang, K.L., Dudek, S.E., Masemann, D., Durán, F.J., et al. "In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B" . PLoS ONE, vol. 10, no. 2, 2015.
http://dx.doi.org/10.1371/journal.pone.0117794
---------- VANCOUVER ----------
Silva, I.T., Carvalho, A., Lang, K.L., Dudek, S.E., Masemann, D., Durán, F.J., et al. In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B. PLoS ONE. 2015;10(2).
http://dx.doi.org/10.1371/journal.pone.0117794