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Induction of apoptosis by new ent-kaurene-type diterpenoids isolated from the New Zealand liverwort Jungermannia species.

Abstract
Some diterpenoids show various biological activities, including anti-inflammatory, anti-HIV and anti-tumor activity. Previously, we have focused our research on the apoptosis-inducing properties of diterpenoids and found that some ent-kaurene-type diterpenoids induced apoptosis in human leukemia HL-60 cells. In this study, we have investigated the induction of apoptosis in HL-60 cells by the novel ent-kaurene-type diterpenoids, jungermannenones A (JA), B (JB), C (JC) and D (JD), isolated from the New Zealand liverwort Jungermannia species. Treatment of the cells with each compound for 12 h resulted in cytotoxicity (IC (50) values: A, 1.3; B, 5.3; C, 7.8; D, 2.7 microM) and caused DNA fragmentation and nuclear condensation, both biochemical markers of the induction of apoptosis. Treatment with the compounds resulted in activation of caspases, including caspase-3 and caspase-8. A broad-spectrum inhibitor of caspases, Z-Asp-CH (2)-DCB, attenuated the cytotoxicity induced by these compounds, suggesting that JA, JB, JC and JD induced apoptosis through a caspase-dependent pathway. JA and JD inhibited the activity of nuclear factor-kappaB, which is a transcriptional factor of anti-apoptotic factors. Thus, some of these new ent-kaurene-type diterpenoids may be promising candidates for anti-tumor agents.
AuthorsMasuo Kondoh, Fumihiro Nagashima, Ikue Suzuki, Motoki Harada, Makiko Fujii, Yoshinori Asakawa, Yoshiteru Watanabe
JournalPlanta medica (Planta Med) Vol. 71 Issue 11 Pg. 1005-9 (Nov 2005) ISSN: 0032-0943 [Print] Germany
PMID16320200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Diterpenes, Kaurane
  • Caspases
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Apoptosis
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Diterpenes, Kaurane (chemistry, isolation & purification, pharmacology)
  • HL-60 Cells
  • Hepatophyta
  • Humans

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