Activation of p38 mitogen-activated protein kinase during ent-11alpha-hydroxy-16-kauren-15-one-induced apoptosis in human leukemia HL-60 cells.

Kaurene-type diterpenes possess various biological activities including antitumor and anti-inflammatory effects. Indeed, we have found that an ent-kaurene diterpene, ent-11alpha-hydroxy-16-kauren-15-one (KD), induced apoptosis via caspase-8 activation in human promyelocytic leukemia HL-60 cells. However, the mechanism of caspase-8 activation by KD is not clear. In this study, we investigated the involvement of p38 mitogen-activated protein kinase (p38 (MAPK)) in KD-induced apoptosis. p38 (MAPK) was activated by treatment with KD parallel to DNA ladder formation. Pretreatment with SB203580, a specific inhibitor of p38 (MAPK), attenuated induction of apoptosis by KD and inhibited activation of caspase-8. Cleavage of Bid, a typical substrate of caspase-8, was also inhibited by treatment with SB203580, suggesting that activation of p38 (MAPK) occurs upstream of caspase-8 during KD-induced apoptosis.
AuthorsMasuo Kondoh, Ikue Suzuki, Motoki Harada, Fumihiro Nagashima, Makiko Fujii, Yoshinori Asakawa, Yoshiteru Watanabe
JournalPlanta medica (Planta Med) Vol. 71 Issue 3 Pg. 275-7 (Mar 2005) ISSN: 0032-0943 [Print] Germany
PMID15770551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Diterpenes, Kaurane
  • Mitogens
  • Plant Extracts
  • p38 Mitogen-Activated Protein Kinases
  • Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Diterpenes, Kaurane (administration & dosage, pharmacology, therapeutic use)
  • HL-60 Cells (drug effects, metabolism)
  • Humans
  • Isodon
  • Mitogens (administration & dosage, pharmacology, therapeutic use)
  • Phytotherapy
  • Plant Extracts (administration & dosage, pharmacology, therapeutic use)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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