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Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation
The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427333/ https://www.ncbi.nlm.nih.gov/pubmed/25961580 http://dx.doi.org/10.1371/journal.pone.0126459 |
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author | Li, Wenjuan Zhang, Chunjing Ren, Amy Li, Teena Jin, Rong Li, Guohong Gu, Xin Shi, Runhua Zhao, Yunfeng |
author_facet | Li, Wenjuan Zhang, Chunjing Ren, Amy Li, Teena Jin, Rong Li, Guohong Gu, Xin Shi, Runhua Zhao, Yunfeng |
author_sort | Li, Wenjuan |
collection | PubMed |
description | The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis. |
format | Online Article Text |
id | pubmed-4427333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44273332015-05-21 Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation Li, Wenjuan Zhang, Chunjing Ren, Amy Li, Teena Jin, Rong Li, Guohong Gu, Xin Shi, Runhua Zhao, Yunfeng PLoS One Research Article The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis. Public Library of Science 2015-05-11 /pmc/articles/PMC4427333/ /pubmed/25961580 http://dx.doi.org/10.1371/journal.pone.0126459 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Li, Wenjuan Zhang, Chunjing Ren, Amy Li, Teena Jin, Rong Li, Guohong Gu, Xin Shi, Runhua Zhao, Yunfeng Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title_full | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title_fullStr | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title_full_unstemmed | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title_short | Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation |
title_sort | shikonin suppresses skin carcinogenesis via inhibiting cell proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427333/ https://www.ncbi.nlm.nih.gov/pubmed/25961580 http://dx.doi.org/10.1371/journal.pone.0126459 |
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