Details

Autor(en) / Beteiligte

• Tung, Shui-Yi
• Lee, Ko-Chao
• Lee, Kam-Fai
• Yang, Ya-Ling
• Huang, Wen-Shih
• Lee, Li-Ya
• Chen, Wan-Ping
• Chen, Chin-Chu
• Teng, Chih-Chuan
• Shen, Chien-Heng
• Hsieh, Meng-Chiao
• Huang, Cheng-Yi
• Sheen, Jiunn-Ming
• Kuo, Hsing-Chun

Titel

Apoptotic mechanisms of gastric cancer cells induced by isolated erinacine S through epigenetic histone H3 methylation of FasL and TRAIL

Ist Teil von

• Food & function, 2021-04, Vol.12 (8), p.3455-3468

Ort / Verlag

England: Royal Society of Chemistry

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Erinacine S, the new bioactive diterpenoid compound isolated from the ethanol extract of the mycelia of Hericium erinaceus , displays great health-promoting properties. However, the effects of erinacine S on inductive apoptosis in cancer cells such as gastric cancer and its molecular mechanisms remain unclear. Our results demonstrated that erinacine S treatment significantly induces cell apoptosis with increased ROS production in gastric cancer cells, but not in normal cells. Significantly, erinacine S also showed its inhibitory effects on tumor growth in an in vivo xenograft mouse model. Furthermore, immunohistochemical analyses revealed that erinacine S treatment significantly increases the FasL and TRAIL protein, whereas it decreases the levels of PCNA and cyclin D1 in the gastric cancer xenograft mice. Consistently, in AGS cells, erinacine S treatment not only triggers the activation of extrinsic apoptosis pathways (TRAIL, Fas-L and caspase-8, -9, -3), but it also suppresses the expression of the anti-apoptotic molecules Bcl-2 and Bcl-XL in a time-dependent manner. In addition, erinacine S also causes cell cycle G1 arrest by the inactivation of CDKs/cyclins. Moreover, our data revealed that activation of the ROS-derived and AKT/FAK/PAK1 pathways is involved in the erinacine S-mediated transcriptional activation of Fas-L and TRAIL through H3K4 trimethylation on their promoters. Together, this study sheds light on the anticancer effects of erinacine S on gastric cancer and its molecular mechanism in vitro and in vivo . Erinacine S, the new bioactive diterpenoid compound isolated from the ethanol extract of the mycelia of Hericium erinaceus , displays great health-promoting properties.