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...
Autores principales: | , , , , , , |
---|---|
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 |