[Apoptosis-inducing properties of ent-kaurene-type diterpenoids from the liverwort Jungermannia truncata].
Ent-11alpha-hydroxy-16-kauren-15-one (1) induced apoptosis in a human leukemia cell line (HL-60 cells), however, the apoptosis-inducing properties of 1 and its related compounds remain to be proved. We examined the involvement of caspases, a family of cysteine aspartic proteases, which play a central role in induction of apoptosis, in apoptosis induced by the compounds in HL-60 cells. Treatment of the cells with compounds 1, 2 and 3 with the enone group at C-15/C-16 caused DNA fragmentation, a sign of induction of apoptosis, and proteolysis of poly(ADP-ribose) polymerase (PARP), a hallmark of caspase activation. Z-Asp-CH2-DCB, abroad spectrum inhibitor of caspases, abolished the appearance of DNA fragmentation and also significantly attenuated the cytotoxic effects. These data suggest that induction of apoptosis by 1 and some of its related compounds are dependent on caspases activation and might be partly involved in the cytotoxicity in HL-60 cells.
Nagashima
Fumihiro
F
Kondoh
Masuo
M
Kawase
Masaki
M
Simizu
Siro
S
Osada
Hiroyuki
H
Fujii
Makiko
M
Watanabe
Yoshiteru
Y
Sato
Masao
M
Asakawa
Yoshinori
Y
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D045786:Diterpenes, Kaurane; D018922:HL-60 Cells / Q000187:drug effects; D035926:Hepatophyta; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010936:Plant Extracts; C002627:kaurene