Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells

作者：Jang Ki Young; Jeong Soo Jin; Kim Sun Hee; Jung Ji Hoon; Kim Ji Hyun; Koh Wonil; Chen Chang Yan; Kim Sung Hoon

来源：Cancer Letters, 2012, 319(2): 197-202.

DOI：10.1016/j.canlet.2012.01.008

• Fisetin
• Apoptosis
• AMPK
• ROS
• Multiple myeloma

We investigated the molecular mechanisms responsible for fisetin-induced apoptosis in U266 cells. Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling. Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1(L), and upregulation of Bax, Rim and Bad. Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of Ala and mTOR. Fisetin also stimulated generation of ROS in U266 cells. Conversely, compound C or N-acetyl-L-cystein blocked fisetin-induced apoptosis. Our data suggest that fisetin-induced apoptosis in U266 cells is through ROS and AMPK pathways.

• 出版日期2012-6-28