Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells

Abstract

Evodiamine (EVO) exhibits strong anti-cancer effects. However, the effect of EVO on the human colorectal cancer cell line HCT-116 has not been explored in detail, and its underlying molecular mechanisms remain unknown. In the present study, cell viability was assessed by Cell Counting Kit-8 (CCK-8). Cell cycle and apoptosis were measured by flow cytometry, and morphological changes in the nucleus were examined by fluorescence microscopy and Hoechst staining. Cell motility was detected by Transwell assay. ELISA was used to assess the protein levels of autocrine motility factor (AMF) in the cell supernatant, and protein expression was determined by Western blotting. Our results showed that EVO inhibited the proliferation of HCT-116 cells, caused accumulation of cells in S and G2/M phases, and reduced the levels of the secreted form of AMF. The protein levels of tumor suppressor protein (p53), Bcl-2 Associated X protein (Bax), B cell CLL/lymphoma-2 (Bcl-2), phosphoglucose isomerase (PGI), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and matrix metalloproteinase 3 (MMP3) were altered in cells treated with EVO. Taken together, our results suggest that EVO modulates the activity of the p53 signaling pathway to induce apoptosis and downregulate MMP3 expression by inactivating the JAK2/STAT3 pathway through the downregulation of PGI to inhibit migration of HCT-116 human colorectal cancer cells.

Induction of apoptosis by ethanol extract of <i>Evodia rutaecarpa</i> in HeLa human cervical cancer cells <i>via</i> activation of AMP-activated protein kinase

“…However, based on our present data showing that z-DEVD-fmk completely blocked the apoptotic cell death induced by EEER, we suggest that the role of AIF and endoG in EEERinduced apoptosis might be slight. Notably, several preceding studies have also reported that evodiamine, an alkaloid isolated from E. rutaecarpa, induced mitochondria-mediated apoptosis in several cancer cell lines (20)(21)(22)(23)(24)(25)(26), which supports our current results.…”

“…In addition, there have been other reports indicating that inhibition of the activity of the mechanistic target of rapamycin (mTOR) signal systems, or insulin-like growth factor 1, is involved in apoptosis of human cancer cells exposed to evodiamine (22,23). Furthermore, it has been reported that the inhibition of human cancer cell proliferation by evodiamine is associated with overcoming of multidrug resistance related to nuclear factor-kappa B signaling pathway inhibition and inhibition of invasive activity by calcium/JNK signaling-mediated autophagy induction and to increases in the activity of matrix metalloproteinase (24)(25)(26) However, to date no systematic study has been conducted on E. rutaecarpa extracts per se. In the current study, we explored the anti-cancer effects of the ethanol extract of E. rutaecarpa immature fruits (EEER) in HeLa human cervical cancer cells and investigated the underlying mechanism.…”

Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells

“…Evodiamine induced cell-cycle arrest at G 2 /M phase in human UCC cells was firstly observed in our study (Figure 3). It also reported in various cancers post-treatment with evodiamine including human leukemic T-lymphocytes, prostate cancer, cervix carcinoma, thyroid cancer, colorectal cancer, ovarian cancer, and lung cancer (10,11,14,15,22,(34)(35)(36)(37)(38). In addition, we and others have demonstrated apoptosis in human UCC and other cancers after evodiamine treatment.…”

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

“…EVO displays antimigratory, anti-invasive, and antimetastatic activity in human lung cancer, breast cancer, and nasopharyngeal cancer cells in vitro and in mouse models. EVO exerts antimetastatic activity by multiple mechanisms, such as regulation of matrix metalloproteinase-3 activity, p38 kinase activity, extracellular signal-regulated kinase activity, and Janus kinase/STAT pathway, and downregulation of phosphoglucose isomerase (Du et al, 2013;Peng et al, 2015;Zhao et al, 2015).…”