Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer.
Gastric cancer is often diagnosed in locally advanced or metastatic stages, which preludes a poor prognosis. As only 10% of patients with advanced gastric cancer treated with chemotherapy survive 2 years, new approaches for preventing and controlling the disease are required. We therefore, assessed in gastric cancer cells the chemotherapeutic potential and mechanism of deguelin, a rotenoid of the flavonoid family isolated from several plant species. The effect of deguelin on the proliferation and apoptosis in the gastric cancer cells were assessed by MTT and flow cytometry. The growth of gastric cancer cells (SNU-484, AGS and MKN-28) was inhibited by deguelin in a dose-dependent manner. G2/M phase arrest was induced by deguelin in gastric cancer cells. deguelin (1 microM) induced chromatin condensation and DNA fragmentation. Also the exposure to 1 microM deguelin resulted in the increase in early-apoptotic cells (Annexin V-positive/Propidium iodide-negative) after 24 h, compared to the cells in the control medium (31 versus 12%). Deguelin-induced apoptosis involved the caspase-9 and caspase-3 pathways in gastric cancer cells. Akt phosphorylation, hypoxia-inducible factor-1alpha accumulation, and vascular endothelial growth factor expression in gastric cancer cells was inhibited by deguelin. Taken together, deguelin showed anticancer activity in gastric cancer cells, which is correlated with the inhibition of angiogenesis and induction of apoptosis. Deguelin may be a potential agent in inhibiting the progression of gastric cancer by virtue of its activity on these crucial cell characteristics.
Lee
Hyunseung
H
Department of Biomedical Sciences and Clinical Research Center, College of Medicine, Inha University, Jung-gu, Incheon 400-712, Republic of Korea.
Lee
Ju-Hee
JH
Jung
Kyung Hee
KH
Hong
Soon-Sun
SS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D012402:Rotenone; C107676:deguelin