Document Detail


A comparison of apoptosis and necrosis induced by ent-kaurene-type diterpenoids in HL-60 cells.
MedLine Citation:
PMID:  15124083     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that ent-11alpha-hydroxy-16-kauren-15-one (KD) induces apoptosis through a caspase-dependent pathway and the induction of apoptosis is dependent on its enone group in human leukemia cells. Here we investigated the abilities of some KD-related compounds with enone group (Fig. 1) to induce apoptosis and to activate some caspases. The IC50 values of ent-kaurene-related compounds possessing the enone group, ent-1beta-hydroxy-9(11),16-kauradien-15-one (1), ent-9(11),16-kauradiene-12,15-dione (2) and the rearranged ent-kaurane-type diterpene (3), against HL-60 cells after 12 h of treatment were 40 microM, 1.8 microM and 5.5 microM, respectively. Although treatment with 3 induced apoptosis, DNA ladder formation was not observed after treatment with 1 or 2. Induction of necrosis, as assayed by trypan blue staining, was observed after treatment with 1 or 2. Treatment with compound 1, 2 or 3 induced proteolysis of poly(ADP-ribose) polymerase (PARP), a substrate of caspase-3, and processing of caspase-3. Activation of caspase-8 and processing of Bid, a typical substrate of caspase-8, were also observed on treatment with these compounds. Pretreatment with a broad-spectrum inhibitor of caspases attenuated apoptosis induced by 3 but not necrosis induced by 1 and 2. In summary, KD-related compounds are a unique family of diterpenes that cause either caspase-dependent apoptotic or necrotic cell death.
Authors:
Ikue Suzuki; Masuo Kondoh; Fumihiro Nagashima; Makiko Fujii; Yoshinori Asakawa; Yoshiteru Watanabe
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Planta medica     Volume:  70     ISSN:  0032-0943     ISO Abbreviation:  Planta Med.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-04     Completed Date:  2004-08-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0066751     Medline TA:  Planta Med     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  401-6     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / administration & dosage,  pharmacology*,  therapeutic use
Apoptosis / drug effects*
Diterpenes, Kaurane / administration & dosage,  pharmacology*,  therapeutic use
HL-60 Cells / drug effects
Hepatophyta*
Humans
Inhibitory Concentration 50
Necrosis
Phytotherapy*
Plant Extracts / administration & dosage,  pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Diterpenes, Kaurane; 0/Plant Extracts

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