细胞凋亡
白血病
肿瘤坏死因子α
细胞培养
癌细胞
药理学
免疫学
癌症
生物
化学
癌症研究
生物化学
遗传学
作者
Hiroo Hasegawa,Yasuaki Yamada,Kanki Komiyama,Masahiko Hayashi,Masami Ishibashi,Tatsushi Yoshida,Toshiyuki Sakai,Takashi Koyano,Toh‐Seok Kam,Ken T. Murata,Kazuyuki Sugahara,Kazuto Tsuruda,Norihiko Akamatsu,Kunihiro Tsukasaki,Masato Masuda,Nobuyuki Takasu,Shimeru Kamihira
出处
期刊:Blood
[American Society of Hematology]
日期:2006-01-15
卷期号:107 (2): 679-688
被引量:63
标识
DOI:10.1182/blood-2005-05-1982
摘要
Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells but not in normal cells and, hence, has emerged as a novel anticancer agent. Previously, we showed that although most adult T-cell leukemia/lymphoma (ATLL) cells express the TRAIL death receptor DR4 (TRAIL-R1) or DR5 (TRAIL-R2), they are resistant to TRAIL. Thus, in this study, we tried to find natural products that can overcome TRAIL resistance. Among more than 150 materials screened, a dihydroflavonol that was extracted from Blumea balsamifera (BB-1) exhibited the most striking synergism with TRAIL. Treatment of the TRAIL-resistant ATLL cell line KOB, with a combination of BB-1 and TRAIL, resulted in apparent apoptosis that was not observed on treatment with either agent alone. Furthermore, pretreatment with BB-1 followed by TRAIL further augmented the synergism. BB-1 increased the level of TRAIL-R2 promoter activity and surface protein expression in a p53-independent manner. TRAIL-R2 siRNA inhibited the synergism, indicating that sensitization was caused by the increase of TRAIL-R2 expression. More interestingly, similar effects were observed in other leukemia cell lines by exactly the same mechanisms. These results suggest that combined treatment with BB-1 and TRAIL may be a new strategy for cancer therapy.
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