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Kondoh, M. et al.

Kondoh, Suzuki, Harada, Nagashima, Fujii, Asakawa, Watanabe,

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.[1]

References

Activation of p38 mitogen-activated protein kinase during ent-11alpha-hydroxy-16-kauren-15-one-induced apoptosis in human leukemia HL-60 cells. Kondoh, M., Suzuki, I., Harada, M., Nagashima, F., Fujii, M., Asakawa, Y., Watanabe, Y. Planta Med. (2005) [Pubmed]

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