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  1. C100 医学部/医学系研究科
  2. C100b 紀要
  3. Nagoya journal of medical science
  4. 82(2)

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.82.2.261
863516f7-f456-4fd1-9e63-b83717015468
名前 / ファイル ライセンス アクション
11_Inoue.pdf 11_Inoue.pdf (27.8 MB)
Item type 紀要論文 / Departmental Bulletin Paper(1)
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
著者 Inoue, Chisato

× Inoue, Chisato

WEKO 99300

Inoue, Chisato

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Sobue, Sayaka

× Sobue, Sayaka

WEKO 99301

Sobue, Sayaka

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Mizutani, Naoki

× Mizutani, Naoki

WEKO 99302

Mizutani, Naoki

Search repository
Kawamoto, Yoshiyuki

× Kawamoto, Yoshiyuki

WEKO 99303

Kawamoto, Yoshiyuki

Search repository
Nishizawa, Yuji

× Nishizawa, Yuji

WEKO 99304

Nishizawa, Yuji

Search repository
Ichihara, Masatoshi

× Ichihara, Masatoshi

WEKO 99305

Ichihara, Masatoshi

Search repository
Takeuchi, Toshiyuki

× Takeuchi, Toshiyuki

WEKO 99306

Takeuchi, Toshiyuki

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Hayakawa, Fumihiko

× Hayakawa, Fumihiko

WEKO 99307

Hayakawa, Fumihiko

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Suzuki, Motoshi

× Suzuki, Motoshi

WEKO 99308

Suzuki, Motoshi

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Ito, Tetsuro

× Ito, Tetsuro

WEKO 99309

Ito, Tetsuro

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Nozawa, Yoshinori

× Nozawa, Yoshinori

WEKO 99310

Nozawa, Yoshinori

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Murate, Takashi

× Murate, Takashi

WEKO 99311

Murate, Takashi

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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 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.
内容記述タイプ Abstract
出版者
出版者 Nagoya University Graduate School of Medicine, School of Medicine
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ departmental bulletin paper
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 ISSN
収録物識別子 0027-7622
ISSN(Online)
収録物識別子タイプ ISSN
収録物識別子 2186-3326
書誌情報 Nagoya Journal of Medical Science

巻 82, 号 2, p. 261-280, 発行日 2020-05
著者版フラグ
値 publisher
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