Authors
Seungwon Ji, Jin-Young Lee, Jan Schrör, Aloran Mazumder, Dong Man Jang, Sébastien Chateauvieux, Michael Schnekenburger, Che Ry Hong, Christo Christov, Hyoung Jin Kang, Youngjo Lee, Byung Woo Han, Kyu-Won Kim, Hee-Young Shin, Mario Dicato, Claudia Cerella, Gabriele M König, Barbora Orlikova, Marc Diederich
Publication date
2018/3/1
Journal
Cancer letters
Volume
416
Pages
109-123
Publisher
Elsevier
Description
Stemphol (STP) is a novel druggable phytotoxin triggering mixed apoptotic and non-apoptotic necrotic-like cell death in human acute myeloid leukemia (AML). Use of several chemical inhibitors highlighted that STP-induced non-canonical programmed cell death was Ca2+-dependent but independent of caspases, poly (ADP-ribose) polymerase-1, cathepsin, or calpains. Similar to thapsigargin, STP led to increased cytosolic Ca2+ levels and computational docking confirmed binding of STP within the thapsigargin binding pocket of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA). Moreover, the inositol 1,4,5-trisphosphate receptor is implicated in STP-modulated cytosolic Ca2+ accumulation leading to ER stress and mitochondrial swelling associated with collapsed cristae as observed by electron microscopy. Confocal fluorescent microscopy allowed identifying mitochondrial Ca2+ overload as initiator …
Scholar articles
S Ji, JY Lee, J Schrör, A Mazumder, DM Jang… - Cancer letters, 2018