Differential induction of apoptosis of leukemic cells by rhizochalin, two headed sphingolipids from sponge and its derivatives.
Two-headed sphingolipids bear a certain similarity with sphingolipids in the structure and but differing from classical sphingolipids in alpha,omega-position of the basic groups. We analyzed the apoptotic effects of some two-headed sphingolipids including rhizochalin (Rhz) and its derivatives isolated from sponge Rhizochalina incrustata on human leukemia HL-60 cells. Direct addition of Rhz induced apoptosis of HL-60 cells. The aglycon of Rhz, which has no galactosyl residue, showed a stronger ability to induce apoptotic activity than Rhz. Rhz congeners with acetate derivatives only weakly induced apoptosis. The usual mitochondrial membrane permeability changes and the decrease of protein levels of procaspases-8, -9, and -3 correlated with the apoptotic activity of Rhzs. These results suggest that derivatives of two-headed sphingolipids potently induce apoptosis in mammalian cells when administered exogenously and this cell death was dependent on caspase activation pathways.
Jin
Jun-O
JO
Department of Biochemistry, School of Medicine, Dong-A University, Busan, Korea.
Shastina
Valeria
V
Park
Joo-In
JI
Han
Jin-Yeong
JY
Makarieva
Tatyana
T
Fedorov
Sergey
S
Rasskazov
Valery
V
Stonik
Valentin
V
Kwak
Jong-Young
JY
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013107:Sphingolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000975:Antioxidants; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D006027:Glycosides; D013107:Sphingolipids; C068290:rhizochaline; D020169:Caspases