https://scholars.lib.ntu.edu.tw/handle/123456789/564835
標題: | Denbinobin induces apoptosis by apoptosis-inducing factor releasing and DNA damage in human colorectal cancer HCT-116 cells | 作者: | Chen T.-H. Pan S.-L. JIH-HWA GUH Chen C.-C. Huang Y.-T. Pai H.-C. Teng C.-M. |
公開日期: | 2008 | 卷: | 378 | 期: | 5 | 起(迄)頁: | 447-457 | 來源出版物: | Naunyn-Schmiedeberg's Archives of Pharmacology | 摘要: | Denbinobin is a phenanthraquinone derivative present in the stems of Ephemerantha lonchophylla. We showed that denbinobin induces apoptosis in human colorectal cancer cells (HCT-116) in a concentration-dependent manner. The addition of a pan-caspase inhibitor (zVAD-fmk) did not suppress the denbinobin-induced apoptotic effect, and denbinobin-induced apoptosis was not accompanied by processing of procaspase-3, -6, -7, -9, and -8. However, denbinobin triggered the translocation of the apoptosis-inducing factor (AIF) from the mitochondria into the nucleus. Small interfering RNA targeting of AIF effectively protected HCT-116 cells against denbinobin-induced apoptosis. Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21 WAF1/CIP1, Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin. Taken together, our findings suggest that denbinobin induces apoptosis of human colorectal cancer HCT-116 cells via DNA damage and an AIF-mediated pathway. These results indicate that denbinobin has potential as a novel anticancer agent. ? 2008 Springer-Verlag. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-54249113934&doi=10.1007%2fs00210-008-0324-5&partnerID=40&md5=ec04fb6a6e8d639265b47bcabd2a01c1 https://scholars.lib.ntu.edu.tw/handle/123456789/564835 |
ISSN: | 281298 | DOI: | 10.1007/s00210-008-0324-5 | SDG/關鍵字: | anthraquinone derivative; apoptosis inducing factor; benzyloxycarbonylvalylalanylaspartyl fluoromethyl ketone; cyclin dependent kinase inhibitor 1; denbinobin; procaspase 3; procaspase 6; procaspase 7; procaspase 8; procaspase 9; protein Bax; protein Noxa; protein p21; protein p53; PUMA protein; small interfering RNA; unclassified drug; animal experiment; animal model; apoptosis; article; cell strain HCT116; colorectal cancer; concentration response; controlled study; DNA damage; drug structure; human; human cell; in vivo study; male; mitochondrial membrane potential; mouse; nonhuman; protein targeting; tumor suppressor gene; tumor volume; upregulation; xenograft; Animals; Anthraquinones; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Inducing Factor; Caspases; Cell Line, Tumor; Colorectal Neoplasms; DNA Damage; Dose-Response Relationship, Drug; Humans; Male; Mice; Mice, SCID; Orchidaceae; Phenanthrenes; Xenograft Model Antitumor Assays |
顯示於: | 藥學系 |
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