Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) presents a significant clinical challenge due to its high mortality and recurrence rates.
• Limited therapeutic options with favorable toxicity profiles exist for HCC treatment.
• Evodiamine (Evo), a natural compound, exhibits anti-cancer properties by modulating signaling pathways like NF-κB and MAPK.

Purpose of the Study:

• To investigate the anti-HCC activity of Evodiamine (Evo).
• To elucidate the role of the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway in Evo's anti-cancer effects.
• To determine if Evo inhibits HCC progression by targeting the NOD1 pathway, thereby suppressing NF-κB and MAPK activation.

Main Methods:

• In vitro studies using HCC cell lines to assess Evo's effects on cell cycle, apoptosis markers (P53, Bax, Bcl-2), and key proteins in the NOD1, NF-κB, and MAPK pathways.
• Treatment with a NOD1 agonist (IE-DAP) to evaluate its impact on Evo's efficacy.
• In vivo studies using a subcutaneous xenograft model to confirm tumor inhibitory effects.

Main Results:

• Evodiamine (Evo) induced G2/M phase cell cycle arrest and apoptosis in HCC cells.
• Evo significantly downregulated NOD1, p-P65, p-ERK, p-p38, and p-JNK, while upregulating IκBα.
• NOD1 agonist treatment attenuated Evo's inhibitory effects on HCC cell proliferation and signaling pathway activation.
• Evo demonstrated significant tumor inhibitory effects in vivo via the NOD1 pathway.

Conclusions:

• Evodiamine (Evo) exhibits potent anti-hepatocellular carcinoma (HCC) activity both in vitro and in vivo.
• The anti-cancer mechanism of Evo involves the suppression of the NOD1 signaling pathway, leading to reduced NF-κB and MAPK activation.
• Evo effectively induces apoptosis and cell cycle arrest in HCC cells, presenting a promising therapeutic candidate.