Anti‐Proliferative Effects of Evodiamine on Human Thyroid Cancer Cell Line ARO

Abstract

The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu-Chu-Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3-(4,5-dimethylthiazol -2-yle)2,5-diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose-dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2-p161 protein, and it was also with a decrease of the expression of cdc2-p15. Furthermore, by using the TUNEL assay, evodiamine-induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase-8, caspase-9, caspase-3, and the cleavage of poly ADP-ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling.

Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling

“…In addition, Takada et al found that EVO exerts apoptotic activity by regulating NF-κB activation, resulting in the inhibition of NF-κB-controlled downstream genes, including cyclin D1, c-Myc, survivin, X chromosome-linked IAP (XIAP), Bcl-2 and Bcl-Xl (43). Numerous experiments have demonstrated that EVO activated initiator caspases (caspase-8 and 9) and/or effector caspases (caspase-3) to induce the apoptosis in a variety of tumor cell lines including human colorectal carcinoma COLO205 and HT-29 cells (44) and human thyroid cancer cell line ARO (45). In addition, another study showed that EVO promoted translocation of apoptosis-inducing factor (AIF) into the nucleus of human leukemia u937 cells (46).…”

Evodiamine inhibits proliferation and induces apoptosis in gastric cancer cells

“…Evodiamine was identified as one of the major active substances of Evodia rutaecarpa (5,9). Previous studies have reported the antitumor activity of evodiamine; one study demonstrated that evodiamine was able to inhibit proliferation of human thyroid cancer cells through cell cycle arrest at M phase and the induction of apoptosis (10). In addition, evodiamine was found to inhibit the growth of prostate cancer cells via the induction of apoptosis (11).…”

Preparation, characterization, and anticancer efficacy of evodiamine-loaded PLGA nanoparticles

“…It has been demonstrated that EVO possessed a plenty of pharmacologic activities, such as anti-obesity, anti-inflammatory , and anti-infectious effect (Li-Weber, 2013;Yu et al, 2013). Furthermore, many studies declared that EVO was a promising anti-tumor agent (Jiang & Hu, 2009), which could suppress proliferation (Chen et al, 2010), induce apoptosis (Rasul et al, 2012), and inhibit metastasis (Takada et al, 2005) of cancer cells. These capabilities were believed to function well through the effects of EVO, which could alter the balance of Bcl2 and Bax gene expression by the caspase pathway in cancer cells (Fei et al, 2003).…”