Antiangiogenesis Efficacy of Ethanol Extract from Amomum tsaoko in Ovarian Cancer through Inducing ER Stress to Suppress p-STAT3/NF-kB/IL-6 and VEGF Loop

Natural plants are considered as a huge treasure for anticancer. Amomum tsaoko, a plant of Zingiberaceae, is used widely as a food and traditional medicine in East Asia. In previous studies, Amomum tsaoko has antitumor effect on liver cancer cells, but the mechanism is not clear. Here, we demonstrated that ethanol extract from Amomum tsaoko (At-EE) could inhibit ovarian cancer and decrease angiogenesis in vivo. At-EE did not influence vascular endothelial cells directly, but decreased IL-6 and VEGF secreted by ovarian cancer cells to inhibit angiogenesis through inhibition of p-STAT3 and NF-kB activation. In addition, we demonstrated that p-STAT3 and NF-kB could adjust each other and IL-6 and VEGF also mediate p-STAT3 and NF-kB too, which created a loop. In addition, At-EE interrupted p-STAT3/NF-kB/IL-6 and VEGF loop through induced ER stress. These results reveal that p-STAT3/NF-kB/IL-6 and VEGF is a cascade amplification loop in ovarian cancer for angiogenesis, and induced ER stress can interrupt it. Taken together, this work explored the anticancer activities of Amomum tsaoko, which could be a potential therapeutic candidate in the treatment of ovarian cancer.