Details

Autor(en) / Beteiligte

• Hu, Likun
• Zhang, Ting
• Liu, Dong
• Guan, Guiwen
• Huang, Jian
• Proksch, Peter
• Chen, Xiangmei
• Lin, Wenhan

Titel

Notoamide-type alkaloid induced apoptosis and autophagy a P38/JNK signaling pathway in hepatocellular carcinoma cells

Ist Teil von

• RSC advances, 2019-06, Vol.9 (34), p.19855-19868

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Bioassay-guided fractionation of a coral-associated fungus Aspergillus ochraceus LZDX-32-15 resulted in the isolation of eleven notoamide-type alkaloids, including four new congeners, namely notoamides W-Z ( 1-4 ). The structures of the new alkaloids were determined by extensive analyses of spectroscopic data (1D and 2D NMR, HRESIMS), while ECD data were used for the configurational assignment. Three alkaloids ( 6 , 10 , 11 ) exerted potent inhibition against a panel of hepatocellular carcinoma (HCC) cell lines with IC 50 values ranging from 0.42 to 3.39 μM, that are comparable to the data for paclitaxel. Notoamide G ( 6 ) inhibited the viability of HepG2 and Huh-7 cells via both apoptosis and autophagy pathways. Notoamide G activated the expression of caspase-3, caspase-8, and caspase-9, in association with the degradation of the downstream gene PARP in a dose-dependent manner, suggesting that notoamide G induced apoptosis via a mitochondrial pathway and a dead receptor-mediated pathway. In addition, notoamide G increased the autophagic vacuole in both HepG2 and Huh-7 cells in a dose-dependent manner after 24 h through the significant upregulation of the key proteins Beclin1 and LC3B. Further investigation revealed that notoamide G promoted P38 and JNK phosphorylation, whereas the total protein of P-38 and JNK was slightly influenced. Accordingly, the antitumor proliferation of notoamide G in HCC cells was mechanistically mediated by apoptosis and autophagy through a P38/JNK signaling pathway, while notoamide G was considered as a potent lead for further development as an antitumor agent. Eleven notoamides including four new congeners were isolated from Aspergillus ochraceus . Notoamide G inhibited the viability of hepatocellular carcinoma cell lines by regulation of apoptosis and autophagy through P38/JNK signaling pathway.