Anti-cancer activity of the cell membrane-permeable phytic acid prodrug

[Display omitted] •Synthesis of a prodrug of IP6 (Pro-IP6) and identification of IP6 generated from Pro-IP6 in cells.•Selective anti-cancer effects including apoptosis and inhibitory effects of Akt activation of Pro-IP6.•Effect of Pro-IP6 to reduce size of cancer in mice with adult T-cell leukemia.•...

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Veröffentlicht in:Bioorganic chemistry 2019-11, Vol.92, p.103240-103240, Article 103240
Hauptverfasser: Masunaga, Takuya, Murao, Naoki, Tateishi, Hiroshi, Koga, Ryoko, Ohsugi, Takeo, Otsuka, Masami, Fujita, Mikako
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Sprache:eng
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Zusammenfassung:[Display omitted] •Synthesis of a prodrug of IP6 (Pro-IP6) and identification of IP6 generated from Pro-IP6 in cells.•Selective anti-cancer effects including apoptosis and inhibitory effects of Akt activation of Pro-IP6.•Effect of Pro-IP6 to reduce size of cancer in mice with adult T-cell leukemia.•Establishment of a new tool to elucidate IP6 biology. Phytic acid (IP6) is an ingredient in cereals and legumes, and limited amounts of this compound are considered to enter the cell and exert anti-cancer effects. These effects have been seen by studying cells treated with around 1–5 mM IP6. However, such a large amount of IP6 chelates metals and changes the pH in cell culture medium. To overcome this problem, we synthesized a prodrug of IP6 (Pro-IP6) and elucidated generation of IP6 from Pro-IP6 in cells. Cellular experiments using Pro-IP6 demonstrated selective anti-cancer effects including apoptosis and inhibition of Akt activation. Furthermore, an in vivo study using mice with adult T-cell leukemia also showed that Pro-IP6 reduced the size of the cancer. Taken together, Pro-IP6 is a useful biological tool and may lead to development of new anti-cancer drugs.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2019.103240