Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/50547
Title: Antiproliferative activity of abietane diterpenoids against human tumor cells
Authors: Burmistrova, Olga
Simões, M. Fátima
Rijo, Patrícia
Quintana, Jose 
Bermejo, Jaime
Estevez, Francisco 
UNESCO Clasification: 32 Ciencias médicas
320101 Oncología
Keywords: Human Leukemia-Cells
Plectranthus-Ornatus
Salvia-Miltiorrhiza
Cytotoxic Activity
Apoptosis, et al
Issue Date: 2013
Project: Evaluación de Potenciales Compuestos Antileucémicos. 
Journal: Journal of Natural Products 
Abstract: 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-x(L) 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 (Delta Psi), and modulated by inhibition of extracellular signal-regulated kinases signaling and the p38 mitogen-activated protein kinase pathway.
URI: http://hdl.handle.net/10553/50547
ISSN: 0163-3864
DOI: 10.1021/np400172k
Source: Journal Of Natural Products[ISSN 0163-3864],v. 76 (8), p. 1413-1423
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