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Vaticanol C, a phytoalexin, induces apoptosis of leukemia and cancer cells by modulating expression of multiple sphingolipid metabolic enzymes
https://doi.org/10.18999/nagjms.82.2.261
https://doi.org/10.18999/nagjms.82.2.261863516f7-f456-4fd1-9e63-b83717015468
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
11_Inoue.pdf (27.8 MB)
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| Item type | 紀要論文 / Departmental Bulletin Paper(1) | |||||
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| 公開日 | 2020-06-01 | |||||
| タイトル | ||||||
| タイトル | Vaticanol C, a phytoalexin, induces apoptosis of leukemia and cancer cells by modulating expression of multiple sphingolipid metabolic enzymes | |||||
| 言語 | en | |||||
| 著者 |
Inoue, Chisato
× Inoue, Chisato× Sobue, Sayaka× Mizutani, Naoki× Kawamoto, Yoshiyuki× Nishizawa, Yuji× Ichihara, Masatoshi× Takeuchi, Toshiyuki× Hayakawa, Fumihiko× Suzuki, Motoshi× Ito, Tetsuro× Nozawa, Yoshinori× Murate, Takashi |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報Resource | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
| 権利情報 | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | vaticanol C | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | apoptosis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | sphingolipid rheostat | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | SPHK | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | GCS | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Resveratrol (RSV) has recently attracted keen interest because of its pleiotropic effects. It exerts a wide range of health-promoting effects. In addition to health-promoting effects, RSV possesses anti-carcinogenic activity. However, a non-physiological concentration is needed to achieve an anti-cancer effect, and its in vivo bioavailability is low. Therefore, the clinical application of phytochemicals requires alternative candidates that induce the desired effects at a lower concentration and with increased bioavailability. We previously reported a low IC50 of vaticanol C (VTC), an RSV tetramer, among 12 RSV derivatives (Ito T. et al, 2003). However, the precise mechanism involved remains to be determined. Here, we screened an in-house chemical library bearing RSV building blocks ranging from dimers to octamers for cytotoxic effects in several leukemia and cancer cell lines and their anti-cancer drug-resistant sublines. Among the compounds, VTC exhibited the highest cytotoxicity, which was partially inhibited by a caspase 3 inhibitor, Z-VAD-FMK. VTC decreased the expression of sphingosine kinase 1, sphingosine kinase 2 and glucosylceramide synthase by transcriptional or post-transcriptional mechanisms, and increased cellular ceramides/dihydroceramides and decreased sphingosine 1-phosphate (S1P). VTC-induced sphingolipid rheostat modulation (the ratio of ceramide/S1P) is thought to be involved in cellular apoptosis. Indeed, exogenous S1P addition modulated VTC cytotoxicity significantly. A combination of SPHK1, SPHK2, and GCS chemical inhibitors induced sphingolipid rheostat modulation, cell growth suppression, and cytotoxicity similar to that of VTC. These results suggest the involvement of sphingolipid metabolism in VTC-induced cytotoxicity, and indicate VTC is a promising prototype for translational research. | |||||
| 言語 | en | |||||
| 出版者 | ||||||
| 出版者 | Nagoya University Graduate School of Medicine, School of Medicine | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | departmental bulletin paper | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| ID登録 | ||||||
| ID登録 | 10.18999/nagjms.82.2.261 | |||||
| ID登録タイプ | JaLC | |||||
| 関連情報 | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/822.html | |||||
| ISSN（print） | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0027-7622 | |||||
| ISSN（Online） | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 2186-3326 | |||||
| 書誌情報 |
en : Nagoya Journal of Medical Science 巻 82, 号 2, p. 261-280, 発行日 2020-05 |
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| 著者版フラグ | ||||||
| 値 | publisher | |||||
