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Pinosylvin enhances leukemia cell death via down‐regulation of AMPKα expression
Author(s) -
Song Jina,
Seo Youngsik,
Park Heonyong
Publication year - 2018
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6156
Subject(s) - programmed cell death , autophagy , ampk , apoptosis , microbiology and biotechnology , cancer research , biology , thp1 cell line , chemistry , protein kinase a , cell culture , kinase , biochemistry , genetics
Resveratrol at high concentrations (50–100 μmol/L) is known to induce cell death in leukemia cells. Here, we investigated whether pinosylvin, a resveratrol analogue, induced cell death in leukemia cells. Cell death was found to be markedly elevated by 50‐ to 100‐μmol/L pinosylvin in THP‐1 and U937 cells. It was also shown that pinosylvin induced caspase‐3 activation, flip‐flop of phosphatidylserine, LC3‐II accumulation, LC3 puncta, and p62 degradation in both THP‐1 and U937 cells. These data indicate that pinosylvin‐induced cell death may occur through apoptosis and autophagy. In addition, we showed that pinosylvin down‐regulates AMP‐activated protein kinase α1 (AMPKα1) in leukemia cells. Therefore, we correlated AMPKα1 down‐regulation and leukemia cell death. AMPKα1 inhibition appeared to decrease pinosylvin‐induced apoptosis and autophagy in leukemia cells, implying that AMPK is a key regulator of leukemia cell death. Moreover, we found that both pinosylvin‐induced autophagy and apoptotic progress were reduced in AMPKα1‐overexpressed leukemia cells, when compared with vector‐transfected cells. Cell death was elevated by AMPKα1 overexpression, whereas pinosylvin‐induced cell death was markedly decreased by caspase‐3 inhibitors or autophagy inhibitors. These results suggest that pinosylvin‐induced depletion of AMPKα1 enhances cell death via apoptosis and autophagy in leukemia cells.