title: Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms.
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.
authors.affiliation: Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University , 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Kuniyoshi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Akinobu
authors.initials: A
authors.lastname: Tanaka
authors.forename: Wakako
authors.initials: W
authors.lastname: Shinobu
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohnuki
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Kondo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D020940:Reishi; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D014315:Triterpenes; D014404:Tubulin; D050257:Tubulin Modulators; C556862:ganoderic acid; D014747:Vinblastine