Deguelin inhibits human hepatocellular carcinoma by antiangiogenesis and apoptosis.
Deguelin is a rotenoid isolated from several plant species, which has been reported to have chemopreventive effects in skin, mammary, colon and lung cancers. The effects of deguelin on the proliferation and apoptosis of hepatic cancer cells were assessed by MTT assay and flow cytometric analysis. The growth of hepatic cancer cells (HepG2, Huh7 and SK-Hep1) was inhibited by deguelin in a dose-dependent manner. HepG2 cells of all the cell lines were the most sensitive to deguelin (IC50 = 0.62 microM). The proportion of sub-G1 apoptotic cells increased from 5.19 to 41.27% by deguelin (0.01-10 microM) treatment for 3 days in the HepG2 cells. The effects of deguelin on anti-angiogenesis of the HepG2 cells were assessed by using Western blot and RT-PCR analysis. Treatment of HepG2 cells with deguelin for 16 h under hypoxia conditions reduced the expression of the hypoxia-inducible factor 1alpha protein and vascular endothelial growth factor mRNA in a dose-dependent manner. In order to investigate whether deguelin shows antiangiogenic activities, we performed in vitro and in vivo angiogenesis assays. In a tube formation assay, deguelin remarkably reduced the capillary network formation of human umbilical vein endothelial cells (HUVECs) on Matrigel beds. Furthermore, deguelin markedly decreased the migration of HUVECs compared to the control and reduced angiogenesis on the CAM of chick embryos. These results suggest that deguelin is potentially useful as a chemotherapeutic agent in hepatocellular carcinoma.
Lee
Ju-Hee
JH
College of Medicine, Inha University, Incheon 400-712, Korea.
Lee
Don-Haeng
DH
Lee
Hyun-Seung
HS
Choi
Joon-Seok
JS
Kim
Kyu-Won
KW
Hong
Soon-Sun
SS
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D012402:Rotenone; C107676:deguelin