Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn
Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cucl) isolated from Wilbrandia ebracteata on human non-small-...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_18119727_v9_n2_p54_Silva |
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todo:paper_18119727_v9_n2_p54_Silva2023-10-03T16:33:00Z Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn Silva, I.T. Teixeira, C.R. Lang, K.L. da Guimaraes, T.R. Dudek, S.E. Durán, F.J. Ludwig, S. Caro, M.S.B. Schenkel, E.P. Simões, C.M.O. Apoptosis Cell cycle arrest Cucurbitacins Lung cancer Signaling pathways cucurbitacin cytochrome c paclitaxel protein bcl 2 protein kinase B STAT3 protein actin filament antiproliferative activity apoptosis article cancer cell cancer inhibition cell proliferation concentration (parameters) controlled study Cucurbitaceae cytosol cytotoxicity down regulation drug mechanism drug structure flow cytometry G2 phase cell cycle checkpoint human human cell lung non small cell cancer mitochondrion plant root protein expression protein phosphorylation protein secretion signal transduction Western blotting Wilbrandia ebracteata Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cucl) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cucl treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cucl significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μiM for 48 and 72 h of treatment, respectively. Additionally, Cucl arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cucl inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cucl could be a potential candidate for cancer chemotherapy agent. © 2013 Academic Journals Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_18119727_v9_n2_p54_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 |
Apoptosis Cell cycle arrest Cucurbitacins Lung cancer Signaling pathways cucurbitacin cytochrome c paclitaxel protein bcl 2 protein kinase B STAT3 protein actin filament antiproliferative activity apoptosis article cancer cell cancer inhibition cell proliferation concentration (parameters) controlled study Cucurbitaceae cytosol cytotoxicity down regulation drug mechanism drug structure flow cytometry G2 phase cell cycle checkpoint human human cell lung non small cell cancer mitochondrion plant root protein expression protein phosphorylation protein secretion signal transduction Western blotting Wilbrandia ebracteata |
| spellingShingle |
Apoptosis Cell cycle arrest Cucurbitacins Lung cancer Signaling pathways cucurbitacin cytochrome c paclitaxel protein bcl 2 protein kinase B STAT3 protein actin filament antiproliferative activity apoptosis article cancer cell cancer inhibition cell proliferation concentration (parameters) controlled study Cucurbitaceae cytosol cytotoxicity down regulation drug mechanism drug structure flow cytometry G2 phase cell cycle checkpoint human human cell lung non small cell cancer mitochondrion plant root protein expression protein phosphorylation protein secretion signal transduction Western blotting Wilbrandia ebracteata Silva, I.T. Teixeira, C.R. Lang, K.L. da Guimaraes, T.R. Dudek, S.E. Durán, F.J. Ludwig, S. Caro, M.S.B. Schenkel, E.P. Simões, C.M.O. Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| topic_facet |
Apoptosis Cell cycle arrest Cucurbitacins Lung cancer Signaling pathways cucurbitacin cytochrome c paclitaxel protein bcl 2 protein kinase B STAT3 protein actin filament antiproliferative activity apoptosis article cancer cell cancer inhibition cell proliferation concentration (parameters) controlled study Cucurbitaceae cytosol cytotoxicity down regulation drug mechanism drug structure flow cytometry G2 phase cell cycle checkpoint human human cell lung non small cell cancer mitochondrion plant root protein expression protein phosphorylation protein secretion signal transduction Western blotting Wilbrandia ebracteata |
| description |
Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cucl) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cucl treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cucl significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μiM for 48 and 72 h of treatment, respectively. Additionally, Cucl arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cucl inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cucl could be a potential candidate for cancer chemotherapy agent. © 2013 Academic Journals Inc. |
| format |
JOUR |
| author |
Silva, I.T. Teixeira, C.R. Lang, K.L. da Guimaraes, T.R. Dudek, S.E. Durán, F.J. Ludwig, S. Caro, M.S.B. Schenkel, E.P. Simões, C.M.O. |
| author_facet |
Silva, I.T. Teixeira, C.R. Lang, K.L. da Guimaraes, T.R. Dudek, S.E. Durán, F.J. Ludwig, S. Caro, M.S.B. Schenkel, E.P. Simões, C.M.O. |
| author_sort |
Silva, I.T. |
| title |
Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| title_short |
Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| title_full |
Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| title_fullStr |
Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| title_full_unstemmed |
Proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (A549 cells) of a novel cucurbitacin from Wilbrandia ebracteata cogn |
| title_sort |
proliferative inhibition and apoptotic mechanism on human non-small-cell lung cancer (a549 cells) of a novel cucurbitacin from wilbrandia ebracteata cogn |
| url |
http://hdl.handle.net/20.500.12110/paper_18119727_v9_n2_p54_Silva |
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