Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms

Jie Liu, Kuniyoshi Shimizu, Akinobu Tanaka, Wakako Shinobu, Koichiro Ohnuki, Takanori Nakamura, Ryuichiro Kondo

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14 Citations (Scopus)

Abstract

Ganoderma fungus (Ganodermataceae) is a multifunctional medicinal mushroom and has been traditionally used for the treatment of various types of disease. Ganoderic acid DM (1) is a representative triterpenoid isolated from G. lingzhi and exhibits various biological activities. However, a universal starting point that triggers multiple signaling pathways and results in multifunctionality of 1 is unknown. Here we demonstrate the important clues regarding the mechanisms underlying multi-medicinal action of 1. We examined structure-activity relationships between 1 and its analogs and found that the carbonyl group at C-3 was essential for cytotoxicity. Subsequently, we used 1-conjugated magnetic beads as a probe and identified tubulin as a specific 1-binding protein. Furthermore, 1 showed a similar Kd to that of vinblastine and also affected assembly of tubulin polymers. This study revealed multiple biological activities of 1 and may contribute to the design and development of new tubulin-inhibiting agents.

Original languageEnglish
Article number905
JournalScientific reports
Volume2
DOIs
Publication statusPublished - Dec 14 2012

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All Science Journal Classification (ASJC) codes

  • General

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