7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line
Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of 7-ketocholesterol (7-KC), cholestane-3β-5α-6β-triol (triol), and a mixture of 5α-cholestane-3β,6β-diol and 5α-...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
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| Series: | Biochemistry and Biophysics Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580818302772 |
| _version_ | 1818359876841111552 |
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| author | Debora Levy Thatiana Correa de Melo Beatriz A. Oliveira Jessica L. Paz Fabio A. de Freitas Cadiele O. Reichert Alessandro Rodrigues Sergio P. Bydlowski |
| author_facet | Debora Levy Thatiana Correa de Melo Beatriz A. Oliveira Jessica L. Paz Fabio A. de Freitas Cadiele O. Reichert Alessandro Rodrigues Sergio P. Bydlowski |
| author_sort | Debora Levy |
| collection | DOAJ |
| description | Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of 7-ketocholesterol (7-KC), cholestane-3β-5α-6β-triol (triol), and a mixture of 5α-cholestane-3β,6β-diol and 5α-cholestane-3β,6α-diol (diol) to promote cell death in a human breast cancer cell line (MDA-MB-231). We determined cell viability, after 24-h incubation with oxysterols. These oxysterols promoted apoptosis. At least part of the observed effects promoted by 7-KC and triol arose from an increase in the expression of the sonic hedgehog pathway mediator, smoothened. However, this increased expression was apparently independent of sonic hedgehog expression, which did not change. Moreover, these oxysterols led to increased expression of LXRα, which is involved in cellular cholesterol efflux, and the ATP-binding cassette transporters, ABCA1 and ABCG1. Diols did not affect these pathways. These results suggested that the sonic hedgehog and LXRα pathways might be involved in the apoptotic process promoted by 7-KC and triol. Keywords: Oxysterol, Apoptosis, Cancer, ABC transporters, Sonic hedgehog, LXRα |
| first_indexed | 2024-12-13T20:51:52Z |
| format | Article |
| id | doaj.art-f33b4dbebe034b8e9718a66f3085a554 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-13T20:51:52Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-f33b4dbebe034b8e9718a66f3085a5542022-12-21T23:31:51ZengElsevierBiochemistry and Biophysics Reports2405-58082019-09-01197-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell lineDebora Levy0Thatiana Correa de Melo1Beatriz A. Oliveira2Jessica L. Paz3Fabio A. de Freitas4Cadiele O. Reichert5Alessandro Rodrigues6Sergio P. Bydlowski7Laboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, BrazilDepartamento de Química, Universidade Federal de Sao Paulo, Diadema, SP, BrazilLaboratory of Genetics and Molecular Hematology (LIM31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, Brazil; Instituto Nacional de Ciencia e Tecnologia em Medicina Regenerativa (INCT-Regenera), CNPq, Brazil; Correspondence to: Department of Hematology, Faculdade de Medicina, Universidade de Sao Paulo, Av.Dr. Enéas de Carvalho Aguiar,155, 1st floor, room 43, 05403-000 São Paulo, SP, Brazil.Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of 7-ketocholesterol (7-KC), cholestane-3β-5α-6β-triol (triol), and a mixture of 5α-cholestane-3β,6β-diol and 5α-cholestane-3β,6α-diol (diol) to promote cell death in a human breast cancer cell line (MDA-MB-231). We determined cell viability, after 24-h incubation with oxysterols. These oxysterols promoted apoptosis. At least part of the observed effects promoted by 7-KC and triol arose from an increase in the expression of the sonic hedgehog pathway mediator, smoothened. However, this increased expression was apparently independent of sonic hedgehog expression, which did not change. Moreover, these oxysterols led to increased expression of LXRα, which is involved in cellular cholesterol efflux, and the ATP-binding cassette transporters, ABCA1 and ABCG1. Diols did not affect these pathways. These results suggested that the sonic hedgehog and LXRα pathways might be involved in the apoptotic process promoted by 7-KC and triol. Keywords: Oxysterol, Apoptosis, Cancer, ABC transporters, Sonic hedgehog, LXRαhttp://www.sciencedirect.com/science/article/pii/S2405580818302772 |
| spellingShingle | Debora Levy Thatiana Correa de Melo Beatriz A. Oliveira Jessica L. Paz Fabio A. de Freitas Cadiele O. Reichert Alessandro Rodrigues Sergio P. Bydlowski 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line Biochemistry and Biophysics Reports |
| title | 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line |
| title_full | 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line |
| title_fullStr | 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line |
| title_full_unstemmed | 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line |
| title_short | 7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line |
| title_sort | 7 ketocholesterol and cholestane triol increase expression of smo and lxrα signaling pathways in a human breast cancer cell line |
| url | http://www.sciencedirect.com/science/article/pii/S2405580818302772 |
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