Abstract
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.
Highlights
Ovarian cancer has high mortality rate among all gynecological tumors in the United States [1]
En, IL-6 and VEGF in conditioned media were detected by ELISA kits. (f ) Cells were incubated with stattic, and Nuclear factor kB (NF-kB) was analyzed by western blot. (g) Cells were incubated with PDTC, and p-STAT3 was analyzed by western blot. (h) Cells were treated with condition media form ovarian cancer cells treated by At-EE in presence or absence of IL-6 and VEGF, and NF-kB and p-STAT3 were analyzed by western blot. e results were similar in at least three independent experiments. ∗p < 0.05. ∗∗p < 0.01
Recurrence, metastasis, and drug resistance are the main features of ovarian cancer [33]
Summary
Ovarian cancer has high mortality rate among all gynecological tumors in the United States [1]. IL-6 and VEGF have been demonstrated for importance in growth, metastasis, and progression in many tumors [6, 7]. STAT3, a member of STAT family, modulates the transcription of genes, which can regulate cell survival, proliferation, metastasis, angiogenesis, autophagy, drug resistance, and immune responses [12, 13]. Nuclear factor kB (NF-kB) is a nuclear transcription factor, which can regulate apoptosis, drug resistance, metastasis, inflammation, and immune responses and is thought to be a regulator for the secretion of cytokines [15, 16]. We demonstrate that Amomum tsaoko has good antitumor effect on ovarian cancer. P-STAT3/NF-kB/IL-6 and VEGF is a cascade amplification loop in ovarian cancer. Amomum tsaoko-induced ER stress interrupts p-STAT3/ NF-kB/IL-6 and VEGF loop to inhibit angiogenesis. Our data will help to find the effective substances and provide assistance for Amomum tsaoko’s subsequent study
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