title: Boesenberols, Pimarane Diterpenes with TRAIL-Resistance-Overcoming Activity from Boesenbergia pandurata.
abstract: TRAIL is a potent and selective inducer of apoptosis in most cancer cells while sparing normal cells, which makes it an attractive target for the development of new cancer therapies. In a screening program on natural resources with the ability to abrogate TRAIL resistance, the bioassay-guided fractionation of Boesenbergia pandurata rhizomes resulted in the isolation of 17 pimarane diterpenes and a monoterpene. Among these, compounds 1-8, named boesenberols A-H, are new pimarane diterpenes. All compounds exhibited TRAIL-resistance-overcoming activity in TRAIL-resistant AGS cells. Subtoxic doses of the major compound 9 sensitized AGS cells to TRAIL-induced apoptosis by up-regulating apoptosis-inducing proteins, such as DR4, DR5, p53, Fas, CHOP, Bak, and cleaved caspases-3, -8, and -9, and down-regulating the levels of cell survival proteins, such as Bcl-2, c-FLIP, and GSK-3β, in TRAIL-resistant AGS cells. Furthermore, compound 9 did not decrease the viability of noncancerous (HEK293) cells at concentrations up to 30 μM.
authors: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.|Pharmacy Discipline, Life Science School, Khulna University , Khulna-9208, Bangladesh.
authors: Utpal K
authors: UK
authors: Karmakar
authors: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors: Naoki
authors: N
authors: Ishikawa
authors: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors: Midori A
authors: MA
authors: Arai
authors: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.|Department of Pharmaceutical Chemistry, University of Dhaka , Dhaka-1000, Bangladesh.
authors: Firoj
authors: F
authors: Ahmed
authors: Temko Corporation , 4-27-4 Honcho, Nakano, Tokyo 164-0012, Japan.
authors: Takashi
authors: T
authors: Koyano
authors: Faculty of Agriculture, Khon Kaen University , Khon Kaen 40002, Thailand.
authors: Thaworn
authors: T
authors: Kowithayakorn
authors: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors: Masami
authors: M
authors: Ishibashi
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000235:genetics; D027343:Rhizome / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013785:Thailand; D030521:Zingiberaceae
chemical_list: D045784:Abietanes; D051017:Apoptosis Regulatory Proteins; D039821:Monoterpenes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D053148:Caspase 3