<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">SEKINE, TAKASHI</style></author><author><style face="normal" font="default" size="100%">TAKAHASHI, JURI</style></author><author><style face="normal" font="default" size="100%">NISHISHIRO, MASAYUKI</style></author><author><style face="normal" font="default" size="100%">ARAI, ATSUHIRO</style></author><author><style face="normal" font="default" size="100%">WAKABAYASHI, HIDETSUGU</style></author><author><style face="normal" font="default" size="100%">KURIHARA, TERUO</style></author><author><style face="normal" font="default" size="100%">KOBAYASHI, MASAKI</style></author><author><style face="normal" font="default" size="100%">HASHIMOTO, KEN</style></author><author><style face="normal" font="default" size="100%">KIKUCHI, HIROTAKA</style></author><author><style face="normal" font="default" size="100%">KATAYAMA, TADASHI</style></author><author><style face="normal" font="default" size="100%">KANDA, YUMIKO</style></author><author><style face="normal" font="default" size="100%">KUNII, SHIRO</style></author><author><style face="normal" font="default" size="100%">MOTOHASHI, NOBORU</style></author><author><style face="normal" font="default" size="100%">SAKAGAMI, HIROSHI</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Tumor-specificity and Type of Cell Death Induced by Trihaloacetylazulenes in Human Tumor Cell Lines</style></title><secondary-title><style face="normal" font="default" size="100%">Anticancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2007-01-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">133-143</style></pages><volume><style face="normal" font="default" size="100%">27</style></volume><issue><style face="normal" font="default" size="100%">1A</style></issue><abstract><style  face="normal" font="default" size="100%">Twenty trihaloacetylazulene derivatives with one atom of fluorine, chlorine, bromine or iodine was investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (gingival fibroblast, HGF; pulp cell, HPC; periodontal ligament fibroblast, HPLF) and four human tumor cell lines (squamous cell carcinoma, HSC-2, HSC-3, HSC-4; promyelocytic leukemia, HL-60). There was no apparent difference in the cytotoxic activity between 2-methoxyazulenes [1a-1e, 2a-2e] and 2-ethoxyazulenes [3a-3e, 4a-4e]. Trichloroacetylazulenes [2a-2e, 4a-4e] generally showed higher cytotoxicity and tumor-specificity (expressed as a TS value) as compared with the corresponding trifluoroacetylazulenes [1a-1e, 3a-3e]. Substitution of chloride [1c, 2c, 3c. 4c], bromide [1d, 2d, 3d, 4d] or iodine [1e, 2e, 3e, 4e] at the C-3 position further enhanced cytotoxic activity against four tumor cell lines, especially HL-60 cells. Among twenty trihaloacetylazulene derivatives, two compounds [2d] and [4c] showed the highest tumor specificity (TS=&gt;3.5 and &gt;2.5, respectively). Compounds [2d] and [4c] induced apoptotic cell death characterized by caspase-3, -8 and -9 activation and internucleosomal DNA fragmentation in HL-60 cells. On the other hand, compounds [2d] and [4c] induced autophagic cell death characterized by lower activation of caspases, lack of DNA fragmentation, vacuolization and autophagosome formation detected by acridine orange and LC3-GFP fluorescence, without the decline of the intracellular concentration of three major polyamines in HSC-4 cells. The cytotoxic activity of [4c], but not [2d], was slightly reduced by 3-methyladenine, an inhibitor of autophagy. These results suggest the diversity of cell death type induced in human tumor cell lines by trihaloacetylazulene derivatives.</style></abstract></record></records></xml>