Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis.
In a previous study, we observed that some synthetic curcumin analogs inhibited complex formations between Fos-Jun heterodimer and activator protein-1 (AP-1) DNA. These curcumin analogs have been observed to repress the AP-1 transcription in AP-1-transfected cells and they also inhibited the increased expression of Jun/AP-1 protein by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the same cells. After the AP-1 inhibition by curcumin analogs in TPA-treated HT-1080 human fibrosarcoma cells, a decrease in mRNA expression of c-jun and MMP3 (stromelysin-1) has been observed. We also observed that curcumin analogs down-regulated the expression of MMP-9 (gelatinase-B), correlating with cellular invasion and migration in conditions such as tumor invasion and metastasis, through the electrophoretic mobility shift assay and gelatin zymography methods. Curcumin analogs showed an inhibitory effect on angiogenesis by various test methods including chicken chorioallantoic membrane assay, wound migration assay, invasion assay, and tube formation assay. Through the reverse transcriptase-polymerase chain reaction experiment, we confirmed that curcumin analogs down-regulated the expression of angiogenesis-associated genes, VEGF and MMP-9.
Hahm
Eun-Ryeong
ER
Division of Chemistry and Molecular Engineering, College of Natural Sciences, Seoul National University, NS 60, San 56-1, Shillim-9-dong, Kwanak-gu, Seoul 151-747, Republic of Korea.
Gho
Yong Song
YS
Park
Seyeon
S
Park
Chihoon
C
Kim
Kyu-Won
KW
Yang
Chul-Hak
CH
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002642:Chick Embryo; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014470:Umbilical Cord / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate