RT Journal Article
SR Electronic
T1 Apoptosis-inducing Activity of Trihaloacetylazulenes against Human Oral Tumor Cell Lines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1917
OP 1923
VO 26
IS 3A
A1 YOSHIAKI AKATSU
A1 NOBUHARU OHSHIMA
A1 YOSHIE YAMAGISHI
A1 MASAYUKI NISHISHIRO
A1 HIDETSUGU WAKABAYASHI
A1 TERUO KURIHARA
A1 HIROTAKA KIKUCHI
A1 TADASHI KATAYAMA
A1 NOBORU MOTOHASHI
A1 YUKO SHOJI
A1 HIDEKI NAKASHIMA
A1 HIROSHI SAKAGAMI
YR 2006
UL http://ar.iiarjournals.org/content/26/3A/1917.abstract
AB 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.