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Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents

Tumor necrosis factor‐α (TNF‐α) is a proinflammatory cytokine playing a part in various pathological states. Non‐toxic inhibitors of TNF‐α release are thought to be promising agents for cancer prevention. We found that the acetone fraction of the tobacco leaf surface lipid containing glucose esters...

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Autores principales: Okabe, Sachiko, Suganuma, Masami, Tada, Yukiko, Ochiai, Yumiko, Sueoka, Eisaburo, Kohya, Hidehiko, Shibata, Akihiro, Takahashi, Masami, Mizutani, Masashi, Matsuzaki, Toshiake, Fujiki, Hirota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926112/
https://www.ncbi.nlm.nih.gov/pubmed/10429660
http://dx.doi.org/10.1111/j.1349-7006.1999.tb00799.x
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author Okabe, Sachiko
Suganuma, Masami
Tada, Yukiko
Ochiai, Yumiko
Sueoka, Eisaburo
Kohya, Hidehiko
Shibata, Akihiro
Takahashi, Masami
Mizutani, Masashi
Matsuzaki, Toshiake
Fujiki, Hirota
author_facet Okabe, Sachiko
Suganuma, Masami
Tada, Yukiko
Ochiai, Yumiko
Sueoka, Eisaburo
Kohya, Hidehiko
Shibata, Akihiro
Takahashi, Masami
Mizutani, Masashi
Matsuzaki, Toshiake
Fujiki, Hirota
author_sort Okabe, Sachiko
collection PubMed
description Tumor necrosis factor‐α (TNF‐α) is a proinflammatory cytokine playing a part in various pathological states. Non‐toxic inhibitors of TNF‐α release are thought to be promising agents for cancer prevention. We found that the acetone fraction of the tobacco leaf surface lipid containing glucose esters and sucrose esters inhibited both TNF‐α release from BALB/3T3 and KATO III cells induced by okadaic acid and tumor promotion by okadaic acid on mouse skin initiated with 7,12‐dimethylbenz(a)anthracene (DMBA). Next, we investigated the inhibition of TNF‐α release with synthetic disaccharide esters, such as 6,6′‐di‐0‐alkanoyl‐α,α‐trehaloses (6,6′‐diester‐trehaloses), 4,4′‐di‐0‐alkanoyl‐α,α‐trehaloses (4,4′‐diester‐trehaloses) and 6,6′‐diamino‐6,6′‐dideoxy‐N, N′‐dial‐kanoyl‐α,α‐trehaloses (6,6′‐diamide‐trehaloses) bearing fatty acids of various chain lengths, and n‐ dodecyl‐β‐D‐maltoside as a disaccharide monoester. 6,6′‐Diester‐trehaloses and 4,4′‐diester‐treha‐loses of C(8) to C(14) fatty acids, 6,6′‐diamide‐trehaloses of C(8) to C(14) fatty acids, and n‐dodecyl‐β‐D‐maltoside all inhibited TNF‐α release in a dose‐dependent manner. The IC(50) values are 7.4‐14.8 μM for 6,6′‐diester‐trehaloses (C(8) to C(12)), 14.6‐21.6 μM 4,4′‐diester‐trehaloses (C(8) to C(12)), 2.9‐15.0 μM for 6,6′‐diamide‐trehaloses (C(8) to C(14)) and 23 μM for dodecyl‐β‐D‐maltoside. Both 6,6′‐di‐O‐octanoyl‐α,α‐trehalose (C(8), designated as SS555) and n‐dodecyl‐β‐D‐maltoside (C(12)) inhibited tumor promotion by okadaic acid on mouse skin initiated with DMBA. Percentages of tumor‐bearing mice in week 15 of tumor promotion were reduced from 60.0 to 13.3 with SS555, and to 46.7 with n‐dodecyl‐β‐D‐maltoside. Moreover, SS555 inhibited TNF‐α gene expression mediated through inhibition of AP‐1 activation, but not NF‐αB activation. This paper reports that diester‐trehaloses of C(8) to C(12) fatty acids and mimics of disaccharide monoesters such as n‐dodecyl‐β‐D‐maltoside appear to be potential cancer‐preventive agents of a new type.
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spelling pubmed-59261122018-05-11 Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents Okabe, Sachiko Suganuma, Masami Tada, Yukiko Ochiai, Yumiko Sueoka, Eisaburo Kohya, Hidehiko Shibata, Akihiro Takahashi, Masami Mizutani, Masashi Matsuzaki, Toshiake Fujiki, Hirota Jpn J Cancer Res Article Tumor necrosis factor‐α (TNF‐α) is a proinflammatory cytokine playing a part in various pathological states. Non‐toxic inhibitors of TNF‐α release are thought to be promising agents for cancer prevention. We found that the acetone fraction of the tobacco leaf surface lipid containing glucose esters and sucrose esters inhibited both TNF‐α release from BALB/3T3 and KATO III cells induced by okadaic acid and tumor promotion by okadaic acid on mouse skin initiated with 7,12‐dimethylbenz(a)anthracene (DMBA). Next, we investigated the inhibition of TNF‐α release with synthetic disaccharide esters, such as 6,6′‐di‐0‐alkanoyl‐α,α‐trehaloses (6,6′‐diester‐trehaloses), 4,4′‐di‐0‐alkanoyl‐α,α‐trehaloses (4,4′‐diester‐trehaloses) and 6,6′‐diamino‐6,6′‐dideoxy‐N, N′‐dial‐kanoyl‐α,α‐trehaloses (6,6′‐diamide‐trehaloses) bearing fatty acids of various chain lengths, and n‐ dodecyl‐β‐D‐maltoside as a disaccharide monoester. 6,6′‐Diester‐trehaloses and 4,4′‐diester‐treha‐loses of C(8) to C(14) fatty acids, 6,6′‐diamide‐trehaloses of C(8) to C(14) fatty acids, and n‐dodecyl‐β‐D‐maltoside all inhibited TNF‐α release in a dose‐dependent manner. The IC(50) values are 7.4‐14.8 μM for 6,6′‐diester‐trehaloses (C(8) to C(12)), 14.6‐21.6 μM 4,4′‐diester‐trehaloses (C(8) to C(12)), 2.9‐15.0 μM for 6,6′‐diamide‐trehaloses (C(8) to C(14)) and 23 μM for dodecyl‐β‐D‐maltoside. Both 6,6′‐di‐O‐octanoyl‐α,α‐trehalose (C(8), designated as SS555) and n‐dodecyl‐β‐D‐maltoside (C(12)) inhibited tumor promotion by okadaic acid on mouse skin initiated with DMBA. Percentages of tumor‐bearing mice in week 15 of tumor promotion were reduced from 60.0 to 13.3 with SS555, and to 46.7 with n‐dodecyl‐β‐D‐maltoside. Moreover, SS555 inhibited TNF‐α gene expression mediated through inhibition of AP‐1 activation, but not NF‐αB activation. This paper reports that diester‐trehaloses of C(8) to C(12) fatty acids and mimics of disaccharide monoesters such as n‐dodecyl‐β‐D‐maltoside appear to be potential cancer‐preventive agents of a new type. Blackwell Publishing Ltd 1999-06 /pmc/articles/PMC5926112/ /pubmed/10429660 http://dx.doi.org/10.1111/j.1349-7006.1999.tb00799.x Text en
spellingShingle Article
Okabe, Sachiko
Suganuma, Masami
Tada, Yukiko
Ochiai, Yumiko
Sueoka, Eisaburo
Kohya, Hidehiko
Shibata, Akihiro
Takahashi, Masami
Mizutani, Masashi
Matsuzaki, Toshiake
Fujiki, Hirota
Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title_full Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title_fullStr Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title_full_unstemmed Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title_short Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor‐α Release Are New Anti‐cancer Agents
title_sort disaccharide esters screened for inhibition of tumor necrosis factor‐α release are new anti‐cancer agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926112/
https://www.ncbi.nlm.nih.gov/pubmed/10429660
http://dx.doi.org/10.1111/j.1349-7006.1999.tb00799.x
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