| A comparison of apoptosis and necrosis induced by ent-kaurene-type diterpenoids in HL-60 cells. | |
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MedLine Citation:
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PMID: 15124083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ikue Suzuki; Masuo Kondoh; Fumihiro Nagashima; Makiko Fujii; Yoshinori Asakawa; Yoshiteru Watanabe |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Planta medica Volume: 70 ISSN: 0032-0943 ISO Abbreviation: Planta Med. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-04 Completed Date: 2004-08-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0066751 Medline TA: Planta Med Country: Germany |
Other Details:
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Languages: eng Pagination: 401-6 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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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:
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0/Antineoplastic Agents, Phytogenic; 0/Diterpenes, Kaurane; 0/Plant Extracts |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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