p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells
Natural products regulate cell growth in response to oncogene activation that induces cell cycle arrest and apoptosis in tumor cell lines. We investigated the mechanisms of caspase activation in human malignant melanoma, A375-S2 cells, by the natural product shikonin, which was isolated from the pla...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319325228 |
| _version_ | 1818579979514937344 |
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| author | Zhen Wu Lijun Wu Linhao Li Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima |
| author_facet | Zhen Wu Lijun Wu Linhao Li Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima |
| author_sort | Zhen Wu |
| collection | DOAJ |
| description | Natural products regulate cell growth in response to oncogene activation that induces cell cycle arrest and apoptosis in tumor cell lines. We investigated the mechanisms of caspase activation in human malignant melanoma, A375-S2 cells, by the natural product shikonin, which was isolated from the plant Lithospermum erythrorhizon SIEB. et ZUCC. Shikonin inhibited cell growth in a time- and dose-dependent manner, which might be mediated through up-regulation of p53 and down-regulation of cyclin-dependent protein kinase 4. Caspase activation was detected in shikonin-induced cell apoptosis, which involved in a post-mitochondrial caspase-9-dependent pathway. Decreased Bcl-2 protein levels and increased Bax protein levels were positively correlated with elevated expression of p53 protein. Apoptosis-inducing factor, another apoptotic protein of mitochondria, partially contributed to shikonin-induced release of cytochrome c. Taken together, shikonin-induced DNA damage activates p53 and caspase-9 pathways. Keywords:: shikonin, cell cycle arrest, apoptosis, caspase, p53 |
| first_indexed | 2024-12-16T07:10:18Z |
| format | Article |
| id | doaj.art-6fb50957565e437da69fbde37c3ed3ef |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-16T07:10:18Z |
| publishDate | 2004-01-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-6fb50957565e437da69fbde37c3ed3ef2022-12-21T22:39:55ZengElsevierJournal of Pharmacological Sciences1347-86132004-01-01942166176p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 CellsZhen Wu0Lijun Wu1Linhao Li2Shin-ichi Tashiro3Satoshi Onodera4Takashi Ikejima5Department of Phytochemistry, Shenyang Pharmaceutical University, Shenyang, 110016, P.R. China; China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P.R. ChinaDepartment of Phytochemistry, Shenyang Pharmaceutical University, Shenyang, 110016, P.R. ChinaChina-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P.R. ChinaDepartment of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Machida, Tokyo 194-8543, JapanDepartment of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Machida, Tokyo 194-8543, JapanChina-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P.R. China; Corresponding author. FAX: +86-24-23844463 E-mail: ikejimat@vip.sina.comNatural products regulate cell growth in response to oncogene activation that induces cell cycle arrest and apoptosis in tumor cell lines. We investigated the mechanisms of caspase activation in human malignant melanoma, A375-S2 cells, by the natural product shikonin, which was isolated from the plant Lithospermum erythrorhizon SIEB. et ZUCC. Shikonin inhibited cell growth in a time- and dose-dependent manner, which might be mediated through up-regulation of p53 and down-regulation of cyclin-dependent protein kinase 4. Caspase activation was detected in shikonin-induced cell apoptosis, which involved in a post-mitochondrial caspase-9-dependent pathway. Decreased Bcl-2 protein levels and increased Bax protein levels were positively correlated with elevated expression of p53 protein. Apoptosis-inducing factor, another apoptotic protein of mitochondria, partially contributed to shikonin-induced release of cytochrome c. Taken together, shikonin-induced DNA damage activates p53 and caspase-9 pathways. Keywords:: shikonin, cell cycle arrest, apoptosis, caspase, p53http://www.sciencedirect.com/science/article/pii/S1347861319325228 |
| spellingShingle | Zhen Wu Lijun Wu Linhao Li Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells Journal of Pharmacological Sciences |
| title | p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells |
| title_full | p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells |
| title_fullStr | p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells |
| title_full_unstemmed | p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells |
| title_short | p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells |
| title_sort | p53 mediated cell cycle arrest and apoptosis induced by shikonin via a caspase 9 dependent mechanism in human malignant melanoma a375 s2 cells |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319325228 |
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