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.