Embelin induces apoptosis of human gastric carcinoma through inhibition of p38 MAPK and NF-κB signaling pathways

Abstract

Embelin is a small-molecule inhibitor of X‑linked inhibitor of apoptosis protein (XIAP), and it induces apoptosis in tumor cells via the inhibition of XIAP. The aim of the present study was to investigate the anticancer effect of embelin on human gastric carcinoma cells and the mechanisms underlying this effect. Cell proliferation of SGC7901 human gastric carcinoma cells was measured using MTT assay, following treatment with embelin (5, 10 and 15 µM) on days 1, 3 and 5. Caspase‑3 and nuclear factor (NF)‑κB p65 activation in SGC7901 cells were assessed using commercial kits. Cellular and nuclear apoptosis were analyzed with an Annexin V‑FITC/PI Apoptosis Detection kit and DAPI staining assay, respectively. Phospho (p)‑p38 mitogen‑activated protein kinase (MAPK), p‑inhibitor of NF‑κB (p‑IκBα) and p‑IκB kinase α/β (p‑IKKα/β) protein expression levels were analyzed with western blot assay. In the present study, treatment with embelin decreased cell proliferation, induced caspase‑3 activation and suppressed NF‑κB p65 activation in SGC7901 cells. Furthermore, embelin administration reduced p‑IκBα and p‑IKKα/β protein expression levels. In conclusion, embelin induces cell apoptosis in human gastric carcinoma through activation of p38 MAPK and inhibition of the NF‑κB signaling pathways. It was further suggested that embelin may be used as a potential drug for the treatment of gastric carcinoma.

Epigenetic Modulation Using Small Molecules - Targeting Histone Acetyltransferases in Disease

“…In addition, it alters musclespecific gene expression in HEK 293T cells [194]. Notably, embelin was not directly related to anti-cancer activity upon HAT inhibition yet, but it is associated with proapoptotic effects in prostate cancer cells (PC-3, DU145, LNCaP-LN3) mediated through modulation of Akt and β-catenin signaling and moreover induces apoptosis in human gastric carcinoma through alteration of p38 MAPK and NF-κB signaling pathways [195,196]. In addition, embelin inhibits cell proliferation, induces apoptosis, and alters expression of pivotal oncogenes in MCF-7 and MDA-MB-231 breast cancer cells [197].…”

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

“…Its activation regulates a variety of cellular behaviors such as cell proliferation, differentiation, and apoptosis. The MAPK signaling pathway, including members p38 and ERK, plays a key role in the ability of bone marrow mesenchymal stem cells to differentiate into osteogenic cells (Jaiswal et al, 2000;Liu et al, 2009), and is related to cell self-renewal (Wang et al, 2016;Xu et al, 2016). Hypoxia can activate the p38/ MAPK and MAPK/ERK signaling pathways (Qiu et al, 2016).…”

Embelin inhibits abdominal aortic aneurysm through decreasing IL‑6‑induced STAT3 and NF‑κB inactivation

“…The results of the present study demonstrated that embelin suppressed p-p38 and NF-κB protein expression in AAA mice. Xu et al (14) suggested that embelin induces apoptosis through inhibition of p38 MAPK and NF-κB signaling pathways in human gastric carcinoma.…”

“…Relevant research revealed that embelin also has antioxidant, hepato-protective, antibacterial, anti-diabetic, and anti-inflammatory effects in other organs (12,13). Embelin additionally blocks the NF-ΚB signaling pathway that is the key protein associated with the ischemia-reperfusion injury-induced inflammatory response (14). The aim of the present study was to elucidate how embelin inhibits AAA and its underlying molecular mechanism.…”