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Silva, I.T.; Geller, F.C.; Persich, L.; Dudek, S.E.; Lang, K.L.; Caro, M.S.B.; Durán, F.J.; Schenkel, E.P.; Ludwig, S.; Simões, C.M.O. "Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549" (2016) Investigational New Drugs. 34(2):139-148
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Abstract:

Summary: Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential. © 2016 Springer Science+Business Media New York.

Registro:

Documento: Artículo
Título:Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549
Autor:Silva, I.T.; Geller, F.C.; Persich, L.; Dudek, S.E.; Lang, K.L.; Caro, M.S.B.; Durán, F.J.; Schenkel, E.P.; Ludwig, S.; Simões, C.M.O.
Filiación:Departamento de Ciências Farmacêuticas, CIF, CCS, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, 88040-900, Brazil
Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
UMYMFOR - Department of Organic Chemistry, Universidad de Buenos Aires, Buenos Aires, Argentina
Institute of Molecular Virology, Center of Molecular Biology of Inflammation, Westfaelische-Wilhelms-University, Muenster, Germany
Palabras clave:Apoptosis; Cucurbitacins; Invasion; Metastasis; 2 deoxy 2 bromocucurbitacin B; 2,16 diacetyl cucurbitacin B; 22 deoxy 22 hydroxy 25 deacetoxy cucurbitacin B; caspase; cucurbitacin; cucurbitacin B; cyclin B1; focal adhesion kinase; gelatinase A; gelatinase B; mitogen activated protein kinase; paclitaxel; unclassified drug; caspase; cucurbitacin; cyclin B1; focal adhesion kinase; gelatinase A; gelatinase B; tumor necrosis factor; A549 cell line; apoptosis; Article; cancer inhibition; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; cell cycle progression; cell migration; cell proliferation; controlled study; down regulation; drug cytotoxicity; drug structure; enzyme activation; human; human cell; IC50; in vitro study; lung cancer; lung metastasis; priority journal; protein expression; signal transduction; A-549 cell line; cell cycle checkpoint; cell motion; chemistry; drug effects; enzymology; Lung Neoplasms; metabolism; non small cell lung cancer; pathology; phosphorylation; tumor invasion; A549 Cells; Apoptosis; Carcinoma, Non-Small-Cell Lung; Caspases; Cell Cycle Checkpoints; Cell Movement; Cell Proliferation; Cucurbitacins; Cyclin B1; Down-Regulation; Focal Adhesion Protein-Tyrosine Kinases; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Phosphorylation; Signal Transduction; Tumor Necrosis Factor-alpha
Año:2016
Volumen:34
Número:2
Página de inicio:139
Página de fin:148
DOI: http://dx.doi.org/10.1007/s10637-015-0317-4
Título revista:Investigational New Drugs
Título revista abreviado:Invest. New Drugs
ISSN:01676997
CODEN:INNDD
CAS:caspase, 186322-81-6; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; mitogen activated protein kinase, 142243-02-5; paclitaxel, 33069-62-4; Caspases; Cucurbitacins; Cyclin B1; Focal Adhesion Protein-Tyrosine Kinases; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Tumor Necrosis Factor-alpha
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676997_v34_n2_p139_Silva

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Citas:

---------- APA ----------
Silva, I.T., Geller, F.C., Persich, L., Dudek, S.E., Lang, K.L., Caro, M.S.B., Durán, F.J.,..., Simões, C.M.O. (2016) . Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549. Investigational New Drugs, 34(2), 139-148.
http://dx.doi.org/10.1007/s10637-015-0317-4
---------- CHICAGO ----------
Silva, I.T., Geller, F.C., Persich, L., Dudek, S.E., Lang, K.L., Caro, M.S.B., et al. "Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549" . Investigational New Drugs 34, no. 2 (2016) : 139-148.
http://dx.doi.org/10.1007/s10637-015-0317-4
---------- MLA ----------
Silva, I.T., Geller, F.C., Persich, L., Dudek, S.E., Lang, K.L., Caro, M.S.B., et al. "Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549" . Investigational New Drugs, vol. 34, no. 2, 2016, pp. 139-148.
http://dx.doi.org/10.1007/s10637-015-0317-4
---------- VANCOUVER ----------
Silva, I.T., Geller, F.C., Persich, L., Dudek, S.E., Lang, K.L., Caro, M.S.B., et al. Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549. Invest. New Drugs. 2016;34(2):139-148.
http://dx.doi.org/10.1007/s10637-015-0317-4