Cargando…

Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60

Spiciformin (1) is a sesquiterpene lactone with a germacrane skeleton that is found in two Tanacetum species endemic to the Canary Islands. In this study, the cytotoxicities of 1 and its acetyl derivative (2) were evaluated against human tumor cells. These sesquiterpene lactones were cytotoxic again...

Descripción completa

Detalles Bibliográficos
Autores principales: Saavedra, Ester, Estévez-Sarmiento, Francisco, Said, Mercedes, Eiroa, José Luis, Rubio, Sara, Quintana, José, Estévez, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215469/
https://www.ncbi.nlm.nih.gov/pubmed/32316340
http://dx.doi.org/10.3390/ijms21082782
_version_ 1783532194825764864
author Saavedra, Ester
Estévez-Sarmiento, Francisco
Said, Mercedes
Eiroa, José Luis
Rubio, Sara
Quintana, José
Estévez, Francisco
author_facet Saavedra, Ester
Estévez-Sarmiento, Francisco
Said, Mercedes
Eiroa, José Luis
Rubio, Sara
Quintana, José
Estévez, Francisco
author_sort Saavedra, Ester
collection PubMed
description Spiciformin (1) is a sesquiterpene lactone with a germacrane skeleton that is found in two Tanacetum species endemic to the Canary Islands. In this study, the cytotoxicities of 1 and its acetyl derivative (2) were evaluated against human tumor cells. These sesquiterpene lactones were cytotoxic against human acute myeloid leukemia (U-937 and HL-60) cells, even in cells over-expressing the pro-survival protein Bcl-2, but melanoma (SK-MEL-1) and human mononuclear cells isolated from blood of healthy donors were more resistant. Both compounds are apoptotic inducers in human leukemia U-937 cells. Cell death was mediated by the processing and activation of initiator and effector caspases and the cleavage of poly(ADP-ribose) polymerase, and it was blocked by a broad-spectrum caspase inhibitor and (in the case of sesquiterpene lactone 2) by the selective caspase-3/7, -8, and -9 inhibitors. In addition, certainly in the case of compound 2, this was found to be associated with a decrease in mitochondrial membrane potential, downregulation of the anti-apoptotic protein Bcl-2, activation of the mitogen-activated protein kinases signaling pathway, and generation of reactive oxygen species. It will, therefore, be relevant to continue characterization of this class of compounds.
format Online
Article
Text
id pubmed-7215469
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72154692020-05-22 Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60 Saavedra, Ester Estévez-Sarmiento, Francisco Said, Mercedes Eiroa, José Luis Rubio, Sara Quintana, José Estévez, Francisco Int J Mol Sci Article Spiciformin (1) is a sesquiterpene lactone with a germacrane skeleton that is found in two Tanacetum species endemic to the Canary Islands. In this study, the cytotoxicities of 1 and its acetyl derivative (2) were evaluated against human tumor cells. These sesquiterpene lactones were cytotoxic against human acute myeloid leukemia (U-937 and HL-60) cells, even in cells over-expressing the pro-survival protein Bcl-2, but melanoma (SK-MEL-1) and human mononuclear cells isolated from blood of healthy donors were more resistant. Both compounds are apoptotic inducers in human leukemia U-937 cells. Cell death was mediated by the processing and activation of initiator and effector caspases and the cleavage of poly(ADP-ribose) polymerase, and it was blocked by a broad-spectrum caspase inhibitor and (in the case of sesquiterpene lactone 2) by the selective caspase-3/7, -8, and -9 inhibitors. In addition, certainly in the case of compound 2, this was found to be associated with a decrease in mitochondrial membrane potential, downregulation of the anti-apoptotic protein Bcl-2, activation of the mitogen-activated protein kinases signaling pathway, and generation of reactive oxygen species. It will, therefore, be relevant to continue characterization of this class of compounds. MDPI 2020-04-16 /pmc/articles/PMC7215469/ /pubmed/32316340 http://dx.doi.org/10.3390/ijms21082782 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Saavedra, Ester
Estévez-Sarmiento, Francisco
Said, Mercedes
Eiroa, José Luis
Rubio, Sara
Quintana, José
Estévez, Francisco
Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title_full Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title_fullStr Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title_full_unstemmed Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title_short Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60
title_sort cytotoxicity of the sesquiterpene lactone spiciformin and its acetyl derivative against the human leukemia cell lines u-937 and hl-60
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215469/
https://www.ncbi.nlm.nih.gov/pubmed/32316340
http://dx.doi.org/10.3390/ijms21082782
work_keys_str_mv AT saavedraester cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT estevezsarmientofrancisco cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT saidmercedes cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT eiroajoseluis cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT rubiosara cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT quintanajose cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60
AT estevezfrancisco cytotoxicityofthesesquiterpenelactonespiciforminanditsacetylderivativeagainstthehumanleukemiacelllinesu937andhl60