1'-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of TRAIL.
A component of a traditional Thai condiment, 1'-acetoxychavicol acetate (ACA), is a natural compound, and it is obtained from rhizomes of the ethno-medicinal plant Languas galanga (Zingiberaceae). Our previous studies showed that ACA dramatically inhibited cellular growth of multiple myeloma cells in vivo and in vitro through the induction of apoptosis in association with the activation of caspase-8, inactivation of NF-kappaB, and down-regulation of anti-apoptotic proteins. Subsequently, we investigated the detailed apoptotic pathway of ACA and further demonstrated that ACA up-regulates the expression of both TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) and TRAIL receptor death receptor 5 (DR5). In addition, TRAIL/R-Fc chimera neutralizes the ACA-induced apoptosis. These results suggest that the death signaling of TRAIL is involved in the ACA-induced apoptosis of myeloma cells, and provide a rationale for the induction of TRAIL/Apo2L by ACA, which could potentially be used as a novel therapeutic agent in patients with multiple myeloma.
Ito
Keisuke
K
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nakazato
Tomonori
T
Murakami
Akira
A
Ohigashi
Hajime
H
Ikeda
Yasuo
Y
Kizaki
Masahiro
M
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000627:therapeutic use; D001592:Benzyl Alcohols; D001854:Bone Marrow Cells / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D053221:TNF-Related Apoptosis-Inducing Ligand; D013729:Terpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000627:therapeutic use; D000093242:Interleukin-6 Inhibitors
D051017:Apoptosis Regulatory Proteins; D001592:Benzyl Alcohols; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; C047948:1'-acetoxychavicol acetate