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Apoptosis-inducing activity of trihaloacetylazulenes against human oral tumor cell lines.

Authors
  • Akatsu, Yoshiaki
  • Ohshima, Nobuharu
  • Yamagishi, Yoshie
  • Nishishiro, Masayuki
  • Wakabayashi, Hidetsugu
  • Kurihara, Teruo
  • Kikuchi, Hirotaka
  • Katayama, Tadashi
  • Motohashi, Noboru
  • Shoji, Yuko
  • Nakashima, Hideki
  • Sakagami, Hiroshi
Type
Published Article
Journal
Anticancer research
Publication Date
Jan 01, 2006
Volume
26
Issue
3A
Pages
1917–1923
Identifiers
PMID: 16827125
Source
Medline
License
Unknown

Abstract

Twenty-six trihaloacetylazulene derivatives were investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (HGF, HPC, HPLF) and four human tumor cell lines (HSC-2, HSC-3, HSC-4, HL-60). The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared to the corresponding trifluoroacetylazulenes [1a-13a]. The trichloroacetylazulenes [1b-13b] also showed higher tumor-specific cytotoxicity (expressed as TS value) than the corresponding trifluoroacetylazulenes [1a-13a]. Especially, 2,3-dimethyl-1-trichloroacetylazulene [5b] and 1,3-ditrichloroacetyl-4,6,8-trimethylazulene [11b] showed the highest cytotoxicity and tumor specificity (TS > 35.6 and > 44.1, respectively). These compounds induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 and HSC-3 cells, but activated caspase-3, -8 and -9 in all of these cells, suggesting the activation of both mitochondria-independent (extrinsic) and dependent (intrinsic) pathways. Western blot analysis showed that two compounds [5b, 11b] slightly increased the intracellular concentration of pro-apoptotic proteins (Bad, Bax) in HSC-2 cells. None of the 26 compounds showed anti-HIV activity. These results suggest [5b] and [11b] as possible candidates for future cancer chemotherapy.

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