Cytotoxic activity of tropolones against human oral tumor cell lines.
Twenty-seven tropolone derivatives were investigated for their tumor-specific cytotoxicity, using 3 normal human cells and 3 human oral tumor cell lines. Tropolone derivatives with phenolic OH group, hinokithiol, its tosylate and methyl ethers have relatively higher tumor specificity. 5-Aminotropolone showed the highest specificity, whereas 2-aminotropone and its derivatives showed little or no specificity. 5-Aminotropolone induced apoptotic cell death characterized by internucleosomal DNA fragmentation and caspase 3 activation in the human promyelocytic leukemic HL-60 cell line. ESR spectroscopy showed that 5-aminotropolone produced radical under alkaline condition, and efficiently scavenged O2- and NO produced by HX-XOD reaction and NOC-7, respectively. These data suggest that 5-aminotropolone may induce cytotoxicity by radical-mediated redox reaction.
Wakabayashi
Hidetsugu
H
Faculty of Science, Josai University, Sakado, Saitama, 350-0295, Japan. hwaka@josai.ac.jp
Yokoyama
Keiko
K
Hashiba
Kana
K
Hashimoto
Ken
K
Kikuchi
Hirotaka
H
Nishikawa
Hirofumi
H
Kurihara
Teruo
T
Satoh
Kazue
K
Shioda
Seiji
S
Muto
Shinji
S
Terakubo
Shigemi
S
Nakashima
Hideki
H
Motohashi
Noboru
N
Sakagami
Hiroshi
H
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009062:Mouth Neoplasms; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D014334:Tropolone