Thyrsiferyl 23-acetate and its derivatives induce apoptosis in various T- and B-leukemia cells.
Thyrsiferyl 23-acetate (TF-23A), a cytotoxic compound from marine red alga, induced a rapid cell death in various leukemic T- and B-cell lines. During incubation of Jurkat cells with TF-23A, condensation and fragmentation of nuclei occurred and clusters composed of uneven small cellular particles were formed. Concentration- and time-dependent DNA fragmentation was also induced by the incubation of the cells with TF-23A. These results demonstrate that the TF-23A-induced cell death follows a typical apoptotic process. The TF-23A-induced apoptosis was prevented by fetal calf serum and insulin, but not by EGF or PDGF. TF-23A and its several analogous compounds showed apoptosis-inducing activity. However, only TF-23A out of these compounds showed an inhibitory activity for protein phosphatase 2A, PP2A. These results strongly suggest that a structure of TF-23A involved in induction of apoptosis is different from that involved in the PP2A inhibition.
Matsuzawa
S
S
Section of Biochemistry, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Kawamura
T
T
Mitsuhashi
S
S
Suzuki
T
T
Matsuo
Y
Y
Suzuki
M
M
Mizuno
Y
Y
Kikuchi
K
K
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D019169:Jurkat Cells; D020014:K562 Cells; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008956:Models, Chemical; D010703:Phorbol Esters / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D054648:Protein Phosphatase 2; D011714:Pyrans / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007328:Insulin; D010703:Phorbol Esters; D010982:Platelet-Derived Growth Factor; D011714:Pyrans; D004815:Epidermal Growth Factor; C091148:thyrsiferyl 23-acetate; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2