title: Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.
abstract: From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kato
authors.forename: Dya Fita
authors.initials: DF
authors.lastname: Dibwe
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Chika
authors.initials: C
authors.lastname: Miyoshi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kadota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification*; D029062:Apocynaceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification*; D008968:Molecular Conformation; D013237:Stereoisomerism; D032365:Wikstroemia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D017705:Lignans; C071942:arctigenin