Daidzein inhibits choriocarcinoma proliferation by arresting cell cycle at G1 phase through suppressing ERK pathway in vitro and in vivo

Abstract

Choriocarcinoma is a highly malignant tumor arising from abnormal gestational trophoblast proliferation. Although chemotherapy has dramatically improved the prognosis, there are still some patients who become drug-resistant or relapse. Daidzein has garnered interest in its antitumor activity especially in proliferation inhibition. However, few reports exist on daidzein effect in growth of choriocarcinoma. Therefore, in this study, we performed in vitro and in vivo experiment in JAR and JEG‑3 to investigate the effect of daidzein in proliferation of choriocarcinoma. Daidzein inhibited cell growth in a time- and dose-dependent way. Cell cycle was arrested at G1 phase and expression of cyclin D1, c-myc, PCNA was reduced while p21 was upregulated during daidzein treatment. At the same time, the expression of p-ERK was downregulated and translocation into nuclear afterwards was also inhibited. Moreover, ERK agonist ceramide C6 abolished daidzein's effects on cell proliferation. Besides, in vivo experiment also showed daidzein's anti-proliferation function as xenografts growth was inhibited and expressions of c-myc, PCNA and p-ERK were suppressed. In conclusion, results in our study demonstrate daidzein can inhibit choriocarcinoma cell proliferation in vitro and in vivo; underlying mechanism behind the inhibitory effects may probably be suppressing ERK pathway and afterwards arresting cell cycle at G1 phase.

Daidzein induces choriocarcinoma cell apoptosis in a dose-dependent manner via the mitochondrial apoptotic pathway

“…In choriocarcinoma, daidzein regulates production of human chorionic gonadotropin (27) and, as demonstrated in the authors' previous study, also inhibits cell proliferation (28). In the present study, in vitro experiments were performed to determine whether daidzein exhibits a pro-apoptotic effect on choriocarcinoma cells.…”

“…Jeschke et al (27) observed a significant concentration-dependent decrease in production of human chorionic gonadotropin in trophoblast cells treated with daidzein. Furthermore, the authors previously demonstrated the anti-proliferation activity of daidzein in choriocarcinoma (28). However, few studies regarding the effect of daidzein on apoptosis have been published.…”

DNA methylation mediated down-regulation of ANGPTL4 promotes colorectal cancer metastasis by activating the ERK pathway

“…Following another 48 h of culture, the transfected cells were harvested and the ANGPTL4 expression was quantified using RT-qPCR. Activation of the ERK pathway was performed by treatment with 10 µM of Ceramide C6 (Santa Cruz Biotechnology, Santa Cruz, CA, USA) 13 . The cells were divided into shCtr group (transfected with silencing negative control plasmid), shANGPTL4 group (transfected with shANGPTL4 plasmid), control group (transfected with negative control overexpression plasmid), ANGPTL4 group (transfected with oe-ANGPTL4 plasmid), and ANGPTL4 + Ceramide C6 group (transfected with oe-ANGPTL4 plasmid + Ceramide C6).…”

Enzymatic Metabolism of Flavonoids by Gut Microbiota and Its Impact on Gastrointestinal Cancer

“…The literature review revealed that flavonoids target and positively affect three pathways in GI cancer. Diazedine could inhibit choriocarcinoma cellular proliferation through the suppression of the extracellular-signal-regulated kinase (ERK) pathway by inhibiting p-ERK expression and translocation, as illustrated in Figure 7 [126]. Additionally, Figure 8 illustrates the mechanisms in which the metastasis of colon cancer was inhibited after the administration of dietary delphinidin.…”