Cargando…
Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts
Chemosensitization of cancer cells with small molecules may improve the therapeutic index of antitumoral agents by making tumor cells sensitive to the drug regimen and thus overcome the treatment resistance and side effects of single therapy. Cell membrane lipid rafts are known to transduce various...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874189/ https://www.ncbi.nlm.nih.gov/pubmed/33585438 http://dx.doi.org/10.3389/fcell.2020.571676 |
_version_ | 1783649540798152704 |
---|---|
author | Mishra, Siddhartha Kumar Bae, Yun Soo Lee, Yong-Moon Kim, Jae-Sung Oh, Seung Hyun Kim, Hwan Mook |
author_facet | Mishra, Siddhartha Kumar Bae, Yun Soo Lee, Yong-Moon Kim, Jae-Sung Oh, Seung Hyun Kim, Hwan Mook |
author_sort | Mishra, Siddhartha Kumar |
collection | PubMed |
description | Chemosensitization of cancer cells with small molecules may improve the therapeutic index of antitumoral agents by making tumor cells sensitive to the drug regimen and thus overcome the treatment resistance and side effects of single therapy. Cell membrane lipid rafts are known to transduce various signaling events in cell proliferation. Sensitizing cancer cells may cause modulation of membrane lipid rafts which may potentially be used in improving anticancer drug response. Cedrol, a natural sesquiterpene alcohol, was used to treat human leukemia K562 and colon cancer HT-29 cell lines, and effects were observed. Cedrol decreased the cell viability by inducing apoptosis in both cell lines by activation of pro-apoptosis protein BID and inhibition of anti-apoptosis proteins Bcl-X(L), Bcl-2, and XIAP. Cedrol activated the caspase-9-dependent mitochondrial intrinsic pathway of apoptosis. Furthermore, cedrol inhibited the levels of pAKT, pERK, and pmTOR proteins as well as nuclear and cytoplasmic levels of the p65 subunit of NF-κB. Cedrol caused redistribution of cholesterol and sphingomyelin contents from membrane lipid raft, which was confirmed by a combined additive effect with methyl-β-cyclodextrin (lipid raft-disrupting agent). Lipid raft destabilization by cedrol led to the increased production of ceramides and inhibition of membrane-bound NADPH oxidase 2 enzyme activity. Cholesterol/sphingomyelin-redistributing abilities of cedrol appear as a novel mechanism of growth inhibition of cancer cells. Cedrol can be classified as a natural lipid raft-disrupting agent with possibilities to be used in general studies involving membrane lipid raft modifications. |
format | Online Article Text |
id | pubmed-7874189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78741892021-02-11 Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts Mishra, Siddhartha Kumar Bae, Yun Soo Lee, Yong-Moon Kim, Jae-Sung Oh, Seung Hyun Kim, Hwan Mook Front Cell Dev Biol Cell and Developmental Biology Chemosensitization of cancer cells with small molecules may improve the therapeutic index of antitumoral agents by making tumor cells sensitive to the drug regimen and thus overcome the treatment resistance and side effects of single therapy. Cell membrane lipid rafts are known to transduce various signaling events in cell proliferation. Sensitizing cancer cells may cause modulation of membrane lipid rafts which may potentially be used in improving anticancer drug response. Cedrol, a natural sesquiterpene alcohol, was used to treat human leukemia K562 and colon cancer HT-29 cell lines, and effects were observed. Cedrol decreased the cell viability by inducing apoptosis in both cell lines by activation of pro-apoptosis protein BID and inhibition of anti-apoptosis proteins Bcl-X(L), Bcl-2, and XIAP. Cedrol activated the caspase-9-dependent mitochondrial intrinsic pathway of apoptosis. Furthermore, cedrol inhibited the levels of pAKT, pERK, and pmTOR proteins as well as nuclear and cytoplasmic levels of the p65 subunit of NF-κB. Cedrol caused redistribution of cholesterol and sphingomyelin contents from membrane lipid raft, which was confirmed by a combined additive effect with methyl-β-cyclodextrin (lipid raft-disrupting agent). Lipid raft destabilization by cedrol led to the increased production of ceramides and inhibition of membrane-bound NADPH oxidase 2 enzyme activity. Cholesterol/sphingomyelin-redistributing abilities of cedrol appear as a novel mechanism of growth inhibition of cancer cells. Cedrol can be classified as a natural lipid raft-disrupting agent with possibilities to be used in general studies involving membrane lipid raft modifications. Frontiers Media S.A. 2021-01-21 /pmc/articles/PMC7874189/ /pubmed/33585438 http://dx.doi.org/10.3389/fcell.2020.571676 Text en Copyright © 2021 Mishra, Bae, Lee, Kim, Oh and Kim. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Mishra, Siddhartha Kumar Bae, Yun Soo Lee, Yong-Moon Kim, Jae-Sung Oh, Seung Hyun Kim, Hwan Mook Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title | Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title_full | Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title_fullStr | Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title_full_unstemmed | Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title_short | Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts |
title_sort | sesquiterpene alcohol cedrol chemosensitizes human cancer cells and suppresses cell proliferation by destabilizing plasma membrane lipid rafts |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874189/ https://www.ncbi.nlm.nih.gov/pubmed/33585438 http://dx.doi.org/10.3389/fcell.2020.571676 |
work_keys_str_mv | AT mishrasiddharthakumar sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts AT baeyunsoo sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts AT leeyongmoon sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts AT kimjaesung sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts AT ohseunghyun sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts AT kimhwanmook sesquiterpenealcoholcedrolchemosensitizeshumancancercellsandsuppressescellproliferationbydestabilizingplasmamembranelipidrafts |