Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells

Abstract

Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti-inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration-dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose-dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin-induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)-JNK and p-p38, and cleaved poly-ADP ribose polymerase, and decreased the levels of Bcl-2 and p-ERK1/2 in a concentration-dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor-inhibitory effect. Immunohistochemical staining revealed elevated expression of p-JNK and p-p38 as well as reduced expression of p-ERK1/2 associated with silymarin-treatment. Silymarin was revealed to reduce tumor growth through inhibition of p-ERK and activation of p-p38 and p-JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.

Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology

“…As anti-apoptotic genes and pro-apoptotic genes, Bax and Bcl-2 are considered critical for apoptosis regulation (27). In addition, Bax forms apoptotic bodies, and when the expression level of caspase-3 is increased, caspase-3 is activated to induce apoptosis (28). After treatment with PA, apoptosis of HGC-27 and NCI-N87 cells was obviously induced.…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Silymarin reduced cell viability and diminished migration of stomach cancer cells through the induction of apoptosis, inhibition of p-ERK and activation of p-p38 and p-JNK. In vivo, silymarin at a concentration of 100 mg/kg reduced tumor volume and induced apoptosis [369]. Additionally, silymarin dose-dependently inhibited cell growth in prostate cancer cells by initiating apoptosis.…”

Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer

“…Two pathways have been found to play critical roles in the induction of apoptosis: (1) death receptor-related extrinsic pathway; (2) mitochondrial-related intrinsic pathway ( Fig. 2 ) [ 37 ]. In the extrinsic pathway, the binding of a death ligand to a death-related receptor located on the cell membrane activates the caspase pathway [ 38 , 39 ].…”

“…In the intrinsic pathway the release of apoptotic-associated mediators from the mitochondria triggers a signaling cascade [ 40 ]. Following the delivery of extracellular stimuli, a signaling cascade involving the nucleus, leads to activation of mitogen-activated protein kinases (MAPK) which regulate cell proliferation, growth, differentiation, and death [ 37 ]. MAPKs include, c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), extracellular signal-regulated protein kinase 1/2 (ERK1/2), and p38 MAPK.…”