Antiproliferative activity of abietane diterpenoids against human tumor cells
In the present study, the cytotoxicity of 30 diterpenoids with an abietane or a halimane skeleton was determined against five human tumor cell lines (HL-60, U937, Molt-3, SK-MEL-1, and MCF-7). Diterpenoids containing an abietane skeleton including taxodone (1) and taxodione (2), as well as the semisynthetic derivatives 12, 14, 15, 17, and 22, were the most cytotoxic compounds for human leukemia cells. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-xL did not confer resistance to abietane diterpene-induced cytotoxicity. Studies performed on HL-60 cells indicated that growth inhibition triggered by compounds 1, 12, 14, and 15 was caused by induction of apoptosis. This was prevented by the nonspecific caspase inhibitor Z-VAD-FMK and, in the case of compounds 14 and 15, reduced by the selective caspase-8 inhibitor Z-IETD-FMK. Cell death induced by these abietane diterpenes was found to be associated with the release of mitochondrial proteins, including cytochrome c, Smac/DIABLO, and AIF (apoptosis-inducing factor), accompanied by dissipation of the mitochondrial membrane potential (ΔΨ), and modulated by inhibition of extracellular signal-regulated kinases signaling and the p38 mitogen-activated protein kinase pathway.
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American Chemical Society
2013-07-18
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dig-ipna-es-10261-1783452020-12-09T16:47:18Z Antiproliferative activity of abietane diterpenoids against human tumor cells Burmistrova, Olga Simões, M. Fátima Rijo, Patrícia Quintana, José Bermejo, Jaime Estévez, Francisco European Commission Instituto Canario de Investigación del Cáncer Ministerio de Ciencia e Innovación (España) In the present study, the cytotoxicity of 30 diterpenoids with an abietane or a halimane skeleton was determined against five human tumor cell lines (HL-60, U937, Molt-3, SK-MEL-1, and MCF-7). Diterpenoids containing an abietane skeleton including taxodone (1) and taxodione (2), as well as the semisynthetic derivatives 12, 14, 15, 17, and 22, were the most cytotoxic compounds for human leukemia cells. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-xL did not confer resistance to abietane diterpene-induced cytotoxicity. Studies performed on HL-60 cells indicated that growth inhibition triggered by compounds 1, 12, 14, and 15 was caused by induction of apoptosis. This was prevented by the nonspecific caspase inhibitor Z-VAD-FMK and, in the case of compounds 14 and 15, reduced by the selective caspase-8 inhibitor Z-IETD-FMK. Cell death induced by these abietane diterpenes was found to be associated with the release of mitochondrial proteins, including cytochrome c, Smac/DIABLO, and AIF (apoptosis-inducing factor), accompanied by dissipation of the mitochondrial membrane potential (ΔΨ), and modulated by inhibition of extracellular signal-regulated kinases signaling and the p38 mitogen-activated protein kinase pathway. This work was supported by grants from the Spanish Ministry of Science and Innovation and from the European Regional Development Fund (SAF2010-21380) and the Instituto Canario de Investigación del Cáncer (awarded to F. E.). Peer Reviewed 2019-03-22T13:10:44Z 2019-03-22T13:10:44Z 2013-07-18 2019-03-22T13:10:44Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1021/np400172k issn: 0163-3864 e-issn: 1520-6025 Journal of Natural Products 76: 1413-1423 (2013) http://hdl.handle.net/10261/178345 10.1021/np400172k http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004837 en Sí open American Chemical Society |
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In the present study, the cytotoxicity of 30 diterpenoids with an abietane or a halimane skeleton was determined against five human tumor cell lines (HL-60, U937, Molt-3, SK-MEL-1, and MCF-7). Diterpenoids containing an abietane skeleton including taxodone (1) and taxodione (2), as well as the semisynthetic derivatives 12, 14, 15, 17, and 22, were the most cytotoxic compounds for human leukemia cells. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-xL did not confer resistance to abietane diterpene-induced cytotoxicity. Studies performed on HL-60 cells indicated that growth inhibition triggered by compounds 1, 12, 14, and 15 was caused by induction of apoptosis. This was prevented by the nonspecific caspase inhibitor Z-VAD-FMK and, in the case of compounds 14 and 15, reduced by the selective caspase-8 inhibitor Z-IETD-FMK. Cell death induced by these abietane diterpenes was found to be associated with the release of mitochondrial proteins, including cytochrome c, Smac/DIABLO, and AIF (apoptosis-inducing factor), accompanied by dissipation of the mitochondrial membrane potential (ΔΨ), and modulated by inhibition of extracellular signal-regulated kinases signaling and the p38 mitogen-activated protein kinase pathway. |
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European Commission |
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European Commission Burmistrova, Olga Simões, M. Fátima Rijo, Patrícia Quintana, José Bermejo, Jaime Estévez, Francisco |
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Burmistrova, Olga Simões, M. Fátima Rijo, Patrícia Quintana, José Bermejo, Jaime Estévez, Francisco |
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Burmistrova, Olga Simões, M. Fátima Rijo, Patrícia Quintana, José Bermejo, Jaime Estévez, Francisco Antiproliferative activity of abietane diterpenoids against human tumor cells |
author_sort |
Burmistrova, Olga |
title |
Antiproliferative activity of abietane diterpenoids against human tumor cells |
title_short |
Antiproliferative activity of abietane diterpenoids against human tumor cells |
title_full |
Antiproliferative activity of abietane diterpenoids against human tumor cells |
title_fullStr |
Antiproliferative activity of abietane diterpenoids against human tumor cells |
title_full_unstemmed |
Antiproliferative activity of abietane diterpenoids against human tumor cells |
title_sort |
antiproliferative activity of abietane diterpenoids against human tumor cells |
publisher |
American Chemical Society |
publishDate |
2013-07-18 |
url |
http://hdl.handle.net/10261/178345 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004837 |
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