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Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols
We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells. In the present study, we investigated the underlying mechanisms and suggest that costunolide induces apoptosis in huma...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926928/ https://www.ncbi.nlm.nih.gov/pubmed/12495472 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01241.x |
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author | Choi, Jung‐Hye Ha, Joohun Park, Jae‐Hoon Lee, Jae Yeol Lee, Yong Sup Park, Hee‐Juhn Choi, Jong‐Won Masuda, Yutaka Nakaya, Kazuyasu Lee, Kyung‐Tae |
author_facet | Choi, Jung‐Hye Ha, Joohun Park, Jae‐Hoon Lee, Jae Yeol Lee, Yong Sup Park, Hee‐Juhn Choi, Jong‐Won Masuda, Yutaka Nakaya, Kazuyasu Lee, Kyung‐Tae |
author_sort | Choi, Jung‐Hye |
collection | PubMed |
description | We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells. In the present study, we investigated the underlying mechanisms and suggest that costunolide induces apoptosis in human promonocytic leukemia U937 cells by depleting the intracellular thiols. Costunolide treatment rapidly depleted the intracellular reduced glutathione (GSH) and protein thiols, and this preceded the occurrence of apoptosis. Pretreatment with sulfhydryl compounds such as GSH, N‐acetyl‐L‐cysteine, dithiothreitol and 2‐mercaptoethanol almost completely blocked the costunolide‐induced apoptosis, highlighting the significance of the intracellular thiol level in the process. Furthermore, overexpression of Bcl‐2 also significantly attenuated the effects of costunolide. The apoptosis‐inducing activity of costunolide is likely to depend on the exomethylene moiety because derivatives in which this group was reduced, such as dihydrocostunolide and saussurea lactone, did not deplete the cellular thiols and showed no apoptotic activity. Taken together, the present study demonstrates that the costunolide‐induced apoptosis depends on intracellular thiols contents, which are modulated by Bcl‐2. |
format | Online Article Text |
id | pubmed-5926928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59269282018-05-11 Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols Choi, Jung‐Hye Ha, Joohun Park, Jae‐Hoon Lee, Jae Yeol Lee, Yong Sup Park, Hee‐Juhn Choi, Jong‐Won Masuda, Yutaka Nakaya, Kazuyasu Lee, Kyung‐Tae Jpn J Cancer Res Article We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells. In the present study, we investigated the underlying mechanisms and suggest that costunolide induces apoptosis in human promonocytic leukemia U937 cells by depleting the intracellular thiols. Costunolide treatment rapidly depleted the intracellular reduced glutathione (GSH) and protein thiols, and this preceded the occurrence of apoptosis. Pretreatment with sulfhydryl compounds such as GSH, N‐acetyl‐L‐cysteine, dithiothreitol and 2‐mercaptoethanol almost completely blocked the costunolide‐induced apoptosis, highlighting the significance of the intracellular thiol level in the process. Furthermore, overexpression of Bcl‐2 also significantly attenuated the effects of costunolide. The apoptosis‐inducing activity of costunolide is likely to depend on the exomethylene moiety because derivatives in which this group was reduced, such as dihydrocostunolide and saussurea lactone, did not deplete the cellular thiols and showed no apoptotic activity. Taken together, the present study demonstrates that the costunolide‐induced apoptosis depends on intracellular thiols contents, which are modulated by Bcl‐2. Blackwell Publishing Ltd 2002-12 /pmc/articles/PMC5926928/ /pubmed/12495472 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01241.x Text en |
spellingShingle | Article Choi, Jung‐Hye Ha, Joohun Park, Jae‐Hoon Lee, Jae Yeol Lee, Yong Sup Park, Hee‐Juhn Choi, Jong‐Won Masuda, Yutaka Nakaya, Kazuyasu Lee, Kyung‐Tae Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title | Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title_full | Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title_fullStr | Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title_full_unstemmed | Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title_short | Costunolide Triggers Apoptosis in Human Leukemia U937 Cells by Depleting Intracellular Thiols |
title_sort | costunolide triggers apoptosis in human leukemia u937 cells by depleting intracellular thiols |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926928/ https://www.ncbi.nlm.nih.gov/pubmed/12495472 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01241.x |
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